👤 Hanqian Xu

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Also published as: Ting-Xin Xu, Shuang Xu, Renyuan Xu, Cheng Xu, Xiao Xu, Jia-Chen Xu, Shengjie Xu, Yanyong Xu, Nong Xu, D-J Xu, Hongfa Xu, Shiyi Xu, Yunjian Xu, Maochang Xu, Lingyan Xu, Guoheng Xu, Zaibin Xu, Yuexuan Xu, Jinhe Xu, Yitong Xu, Yaping Xu, Miao Xu, Hongming Xu, Jiang Xu, Feng-Qin Xu, Zaihua Xu, Yaru Xu, Qiuyu Xu, Mingcong Xu, Yuanzhong Xu, Mai Xu, Biao Xu, Jingjun Xu, Shuwan Xu, Ya-Ru Xu, Zhilong Xu, Jun-Chao Xu, Shutao Xu, TianBo Xu, Jinyu Xu, Jie-Hua Xu, Peng Xu, Guo-Xing Xu, Yushan Xu, Yongsong Xu, Xin-Rong Xu, Xiang-Min Xu, Bilin Xu, Xiaolong Xu, Jinchao Xu, Han Xu, Xuting Xu, Yu Xu, Yingqianxi Xu, Yanyang Xu, Aili Xu, Weizhi Xu, Peidi Xu, Tongyang Xu, Tieshan Xu, Jianping Xu, Wen-Juan Xu, Bing Xu, Chengyun Xu, Xiaofeng Xu, Zhengang Xu, Guang-Hong Xu, Fangui Xu, Shan-Shan Xu, Song-Song Xu, Hailiang Xu, Quanzhong Xu, Mengqi Xu, Gezhi Xu, Dawei Xu, Linyan Xu, Meishu Xu, Tonghong Xu, Yidan Xu, Panpan Xu, Keli Xu, Xiufeng Xu, Hongwen Xu, Hanyuan Xu, Liang Xu, Zaoyi Xu, Fengqin Xu, Run-Xiang Xu, Xiaoyan Xu, Ruxiang Xu, Huiming Xu, Daqian Xu, Qin-Zhi Xu, Boming Xu, Jiancheng Xu, Zihao Xu, Jinghong Xu, Aimin Xu, Renfang Xu, Ran Xu, Di-Mei Xu, Xiang-liang Xu, Yana Xu, Richard H Xu, Yanchang Xu, Danyi Xu, Lingli Xu, Chengqi Xu, Xiaocheng Xu, Xiaoshuang Xu, H X Xu, Min Xu, Ya'nan Xu, Zhi Ping Xu, Zihe Xu, Hongle Xu, Xuan Xu, Jielin Xu, Yuping Xu, Limin Xu, Yinli Xu, Renshi Xu, Da Xu, C C Xu, Yongqing Xu, Heping Xu, Yiquan Xu, Weilan Xu, Jingjing Xu, Yangxian Xu, Yifan Xu, Congjian Xu, Wentao Xu, Binqiang Xu, Yuerong Xu, Jiaqi Xu, Shang-Fu Xu, Jiachi Xu, Yuejuan Xu, Zhi-Qing David Xu, Chao Xu, Yi-Xian Xu, Longfei Xu, Ziwei Xu, Mengyue Xu, Jingying Xu, Wenhui Xu, Zi-Xiang Xu, Caixia Xu, Chenjie Xu, Xiaoting Xu, Jiacheng Xu, Chunhui Xu, Chengxun Xu, Hengyi Xu, Songsong Xu, Lingyao Xu, Qingqiu Xu, Gangchun Xu, Yanjun Xu, Qiong Xu, Wenxuan Xu, Zifan Xu, Jiayunzhu Xu, Yifeng Xu, DongZhu Xu, Lingna Xu, Qianzhu Xu, Bocheng Xu, Qingjia Xu, Yanni Xu, Li-Yan Xu, Benhong Xu, Fang Xu, Xingsheng Xu, Geyang Xu, Anqi Xu, Zeao Xu, Mengsi Xu, Jun Xu, Qiuhong Xu, Ning'an Xu, Lian-Wei Xu, H F Xu, Hua Xu, Danping Xu, Xiaofang Xu, Shanshan Xu, Sheng-Qian Xu, Bingxin Xu, Ke Xu, Shiqing Xu, Cunshuan Xu, Guangwei Xu, Changwu Xu, Beibei Xu, Zhuangzhuang Xu, Chong-Feng Xu, Yunyi Xu, Yunxuan Xu, Zeya Xu, Jinshu Xu, Laizhi Xu, Xinyu Xu, Meiyu Xu, Bi-Yun Xu, Mingliang Xu, Bingfang Xu, Weixia Xu, Suling Xu, W W Xu, Lidan Xu, Chengkai Xu, Feng Xu, Yunhe Xu, Zesheng Xu, Li Xu, Song Xu, Yungen Xu, Yaobo Xu, Qinli Xu, Yi-Liang Xu, Tan Xu, Dong Xu, Ruiling Xu, Wanqi Xu, Ziyang Xu, Xiaohong Ruby Xu, Guangyu Xu, Xiao-Shan Xu, Wenxin Xu, Yongsheng Xu, Jingya Xu, Zhong-Hua Xu, Jiajie Xu, Dan Xu, Youjia Xu, Longsheng Xu, Mengjie Xu, Guo-Tong Xu, Ting Xu, Chunwei Xu, Tianmin Xu, Xianghong Xu, Nenggui Xu, Hongxia Xu, Meixi Xu, Rongying Xu, Guoliang Xu, Lisi Xu, Leisheng Xu, Yurui Xu, Xianli Xu, Honglin Xu, Yunfang Xu, Guo Xu, Shengyu Xu, Kelin Xu, Xiaoqin Xu, Zheng Xu, Junchang Xu, Jiaying Xu, Beisi Xu, Chunyu Xu, Zhen-Guo Xu, Haonan Xu, Tianyi Xu, Haiman Xu, Lili Xu, Yi Xu, Dongju Xu, Qihang Xu, Zhongwei Xu, Zihua Xu, Qikui Xu, Zhijie Xu, Li-Jun Xu, Qi-Qi Xu, Hanchen Xu, Yaqi Xu, Daohua Xu, Shaonian Xu, Xihui Xu, D Xu, Ziqi Xu, Tian-Ying Xu, Xiangbin Xu, Chen-Run Xu, Jianjuan Xu, Bin Xu, Zhanyu Xu, Lingjuan Xu, Wenjie Xu, Shuwen Xu, Yu-Ming Xu, Cian Xu, Qiulin Xu, Zeyu Xu, Jia Xu, Zengliang Xu, Yujie Xu, Yuting Xu, Jing-Yi Xu, Jiajia Xu, Xiqi Xu, Leiyu Xu, Shi-Na Xu, Ruonan Xu, Wenhuan Xu, Bai-Hui Xu, Jishu Xu, Xiangyu Xu, Lu-Lu Xu, Shiyun Xu, Huaxiang Xu, Lei Xu, Yuli Xu, Chan Xu, Tengfei Xu, Yong Xu, Xuejun Xu, Hang Xu, Junjie Xu, Jinjie Xu, Haoda Xu, Rui-Ming Xu, Yunxi Xu, Jinghua Xu, Ye Xu, Jiyi Xu, Jianyong Xu, Mei-Jun Xu, Yingzheng Xu, Kaiyue Xu, Yeqiu Xu, Songli Xu, Chenqi Xu, Cheng-Jian Xu, Qiaoshi Xu, Rongrong Xu, YanFeng Xu, Jin Xu, Huimian Xu, Zaikun Xu, Aixiao Xu, Yanfei Xu, Chunlin Xu, Huiqiong Xu, Dapeng Xu, Fengxia Xu, Yongmei Xu, Yubin Xu, Xiaojing Xu, Xiaoli Xu, Pu Xu, Wenming Xu, Wenjuan Xu, Wenjing Xu, Haijin Xu, Yawei Xu, Chuanrui Xu, Wenping Xu, Tongtong Xu, Zhigang Xu, Yinfeng Xu, Zi-Hua Xu, Jiean Xu, Ming Xu, Keshu Xu, Weili Xu, Guofeng Xu, Ai-Guo Xu, Xingyu Xu, Shujing Xu, Weiqun Xu, Wen-Hao Xu, Hong-wei Xu, Jianfeng Xu, Y Xu, Steven Jing-Liang Xu, Fangfang Xu, Xiao-Dan Xu, Keyun Xu, Yetao Xu, Qianhui Xu, Chaoqun Xu, Fenghuang Xu, Yuzhi Xu, Tengxiao Xu, Zelin Xu, Xueni Xu, Jing-Ying Xu, Yichi Xu, Ruifeng Xu, Kewei Xu, Fang-Fang Xu, Jiapeng Xu, Sifan Xu, Pengli Xu, Jiaqin Xu, Xiaotao Xu, Chunming Xu, X Xu, Xinyin Xu, Gang Xu, Wei Xu, Yuzhen Xu, Wancheng Xu, Qiming Xu, Hailey Xu, Yuanyuan Xu, Xiaoming Xu, Yimeng Xu, Shihao Xu, Zhipeng Xu, Minxuan Xu, Haowen Xu, Dilin Xu, Rui Xu, Jingzhou Xu, Qiongying Xu, Zhengshui Xu, Jinyi Xu, Q P Xu, Yongjian Xu, Qiushi Xu, Junfei Xu, Mengjun Xu, Hui Ming Xu, Yanzhe Xu, Xiaolei Xu, Qin Xu, Zichuan Xu, Xinyun Xu, Xiaoge Xu, Tianyu Xu, Yigang Xu, Hongyan Xu, Lanjin Xu, Guowang Xu, Jingjie Xu, Yangyang Xu, Yi-Huan Xu, Guanhua Xu, Hongrong Xu, Fen Xu, Jian Xu, Pin-Xian Xu, Tiantian Xu, Zhonghui Xu, Changfu Xu, Dong-Hui Xu, Yi-Ni Xu, Jialu Xu, Yuzhong Xu, Hongli Xu, Mingyuan Xu, Minghao Xu, C F Xu, Qinghua Xu, Yiting Xu, Qian Xu, Jiahong Xu, Haixiang Xu, Xizheng Xu, Kun Xu, Yunfei Xu, Xiaoyang Xu, Xiaojun Xu, Xinyuan Xu, Chen Xu, Guogang Xu, Lingyi Xu, Jinguo Xu, Guiyun Xu, Wenbin Xu, Chunjie Xu, Cheng-Bin Xu, Manman Xu, Dongke Xu, Jia-Mei Xu, Bing-E Xu, Lijiao Xu, You-Song Xu, Mengmeng Xu, Yu-Xin Xu, Jianwei Xu, Kuanfeng Xu, Chun Xu, Shiliyang Xu, Waner Xu, Zhiyao Xu, Gu-Feng Xu, Wenyuan Xu, J T Xu, Chaohua Xu, Haifeng Xu, Ling Xu, Lisha Xu, Huaisha Xu, Xiayun Xu, Qian-Fei Xu, Jinying Xu, Tengyun Xu, Chaoguang Xu, Fuyi Xu, Shihui Xu, Yingna Xu, Aishi Xu, Yanyan Xu, Qiuhui Xu, Bilian Xu, Qinwen Xu, Jinsheng Xu, Tianfeng Xu, Liyi Xu, Lihui Xu, Guanyi Xu, Wenyan Xu, Ru-xiang Xu, Zongzhen Xu, Nan Xu, Jinxian Xu, Rui-Xia Xu, Zhiting Xu, Jiaming Xu, Yi-Tong Xu, Shan-Rong Xu, Xiaojuan Xu, Guifa Xu, Xia-Jing Xu, Libin Xu, Dequan Xu, Guoxu Xu, Hong Xu, Lubin Xu, Cai Xu, Mengying Xu, Tian-Le Xu, J Xu, Weidong Xu, Chengbi Xu, Yibin Xu, Cong-jian Xu, Qianlan Xu, Tingting Xu, Caiqiu Xu, Hong-Yan Xu, Xiao Le Xu, Bei Xu, Jianxin Xu, Guanlan Xu, Ming-Zhu Xu, Long Xu, Xiaopeng Xu, Yinjie Xu, Shufen Xu, Zhihua Xu, Ming-Jiang Xu, Di Xu, Qingwen Xu, Jiake Xu, Tingxuan Xu, Peng-Ju Xu, Ping Xu, Shang-Rong Xu, Li-Zhi Xu, Baoping Xu, Huan Xu, Wenwu Xu, Zhenyu Xu, Chong Xu, Sihua Xu, Anlong Xu, Lu Xu, Chen-Yang Xu, Xiaoyu Xu, Zhe Xu, Qiuyue Xu, Guangquan Xu, Huihui Xu, Peiyu Xu, Ding Xu, Yuchen Xu, Jianguo Xu, Lingyang Xu, Xuegong Xu, Jia-Yue Xu, Liping Xu, Yiyi Xu, Yuling Xu, Jianqiu Xu, Lichi Xu, Xiaojiang Xu, Xiao-Hui Xu, Mao Xu, Yuyang Xu, Zhaofa Xu, Qingchan Xu, Yanli Xu, Julie Xu, Minglan Xu, G Xu, Yali Xu, Miaomiao Xu, Yao Xu, Yanqi Xu, Tian Xu, Xiaojin Xu, Xiaowen Xu, Qing-Yang Xu, Lingxiang Xu, Jianguang Xu, Zhanchi Xu, Shiwen Xu, Haikun Xu, Hongbei Xu, Yixin Xu, Zhan Xu, Fangmin Xu, Xingshun Xu, Wenzhuo Xu, Fu Xu, Haimin Xu, Jiahui Xu, Shengtao Xu, Zhiwei Xu, Peiwei Xu, Daichao Xu, Wen-Hui Xu, Xingyan Xu, H Eric Xu, Zhi-Feng Xu, Mingming Xu, Hongtao Xu, Daiqi Xu, Keman Xu, Yinying Xu, Yuexin Xu, Yuanwei Xu, Xuanqi Xu, Jinfeng Xu, L Xu, Chunyan Xu, Hanting Xu, Chaoyu Xu, Shendong Xu, Tiancheng Xu, Chentong Xu, Guangsen Xu, Yaozeng Xu, Banglao Xu, Danyan Xu, Tao Xu, Ren-He Xu, Haiyan Xu, Jian-Guang Xu, Yu-Fen Xu, Youzhi Xu, Hui Xu, Enwei Xu, F F Xu, Ningda Xu, Zejun Xu, Li-Wei Xu, N Y Xu, Xiaoya Xu, Ren Xu, Ze-Jun Xu, Yanan Xu, Jiapei Xu, Peigang Xu, Tianxiang Xu, Haiqi Xu, Qing-Wen Xu, Junnv Xu, Tian-Rui Xu, Wanfu Xu, Wang-Hong Xu, Maotian Xu, Suoyu Xu, Mingli Xu, Liwen Xu, Qingqing Xu, Zhenming Xu, Jingyi Xu, Yihua Xu, Dong-Juan Xu, Mu Xu, Meifeng Xu, Li-Ling Xu, Dongmei Xu, Jianliang Xu, Xinjie Xu, Pengfei Xu, Changlin Xu, Shuai Xu, Fang-Yuan Xu, Yingli Xu, Ying Xu, Guo-Liang Xu, Zhiqiang Xu, Xirui Xu, Haiying Xu, Wen Xu, Xiaoyin Xu, Wenwen Xu, Mengping Xu, Jing-Yu Xu, Chunlan Xu, Danfeng Xu, Yuan Xu, Wenchun Xu, Zekuan Xu, Nuo Xu, Shuxiang Xu, Min Jie Xu, Penghui Xu, Zixuan Xu, Bingqi Xu, Hongen Xu, Zongli Xu, Tianli Xu, Bo Xu, Qingyuan Xu, Zhaojun Xu, Min-Xuan Xu, Shuhua Xu, Xu Xu, Runhao Xu, M Xu, Xiongfei Xu, Zhaoyao Xu, Yayun Xu, Yingju Xu, Guang-Qing Xu, Kaixiang Xu, Lingling Xu, Jiyu Xu, Anton Xu, Jason Xu, Donghang Xu, Xiaowu Xu, Fengzhe Xu, Xia Xu, Xiangshan Xu, Wan-Ting Xu, Fengyan Xu, Qingheng Xu, Changlu Xu, Huaiyuan Xu, Jinsong Xu, Dongchen Xu, Rang Xu, Peng-Yuan Xu, Jinyuan Xu, Weihong Xu, Wanxue Xu, Xinyi Xu, Jie Xu, Junfeng Xu, Danning Xu, Haiming Xu, Sutong Xu, Shan Xu, Meng Xu, Yueyue Xu, Jixuan Xu, Hongjian Xu, Zhidong Xu, Jinjin Xu, Xiaobo Xu, Hongmei Xu, Shu-Xian Xu, Chuang Xu, Shuaili Xu, Zhixian Xu, Yun Xu, Yue Xu, George X Xu, Man Xu, Jiaai Xu, Zeqing Xu, Baijie Xu, Zheng-Fan Xu, Bojie Xu, Mengru Xu, H Y Xu, Yinhe Xu, Linna Xu, Liqun Xu, Zhi-Zhen Xu, Xiaohui Xu, Xingmeng Xu, Yinxia Xu, Pan Xu, Pengjie Xu, Kai Xu, Kexin Xu, Xiaolin Xu, Cun Xu, Yuxiang Xu, Tong Xu, Jingyu Xu, Li-Li Xu, Yancheng Xu, Chunxiao Xu, Yan Xu, Huajun Xu, Shuiyang Xu, Hongjiang Xu, Kaihao Xu, Suo-Wen Xu, Heng Xu, Zebang Xu, Hongbo Xu, Chenhao Xu, Fanghua Xu, Yaowen Xu, Jing Xu, Qianqian Xu, Andrew Z Xu, Flora Mengyang Xu, Yuanzhi Xu, Leilei Xu, Leyuan Xu, M-Y Xu, Hongzhi Xu, Zongren Xu, Xinyue Xu, Qingxia Xu, Xiao-Hua Xu, Cineng Xu, Nannan Xu, Guoshuai Xu, Mingzhu Xu, X S Xu, Guang Xu, Zhiyang Xu, Song-Hui Xu, Wang-Dong Xu, De-Xiang Xu, Yi Ran Xu, Shengen Xu, Jianzhong Xu, F Xu, Dexiang Xu, Rui-Hua Xu, Tongxin Xu, Wanting Xu, Bingqian Xu, Yang Xu, Jiaqian Xu, Yu-Ping Xu, Zhanqiong Xu, Haixia Xu, Hao Xu, HuiTing Xu, Hanfei Xu, Shu-Zhen Xu, Zhong Xu, Xun Xu, Xiaolu Xu, S Xu, Guangyan Xu, Ning Xu, Chengye Xu, Xizhan Xu, Ya-Peng Xu, Jianming Xu, Wenhao Xu, Minghong Xu, Mingqian Xu, Yaqin Xu, Chang-Qing Xu, Weiyong Xu, Huixuan Xu, Jialin Xu, Z Xu, Fei Xu, Pao Xu, Youping Xu, Keke Xu, Shunjiang Xu, Feilai Xu, Jia-Li Xu, Yucheng Xu, Qi Xu, Jinhua Xu, Chunli Xu, Zhiliang Xu, Jinxin Xu, Bingqing Xu, Lifen Xu, Lianjun Xu, Weihai Xu, Wenqi Xu, Zheng-Hong Xu, Lin Xu, Zuojun Xu, Yanquan Xu, Mingjie Xu, Yanwu Xu, Hui-Lian Xu, Cong Xu, Dongjun Xu, Maodou Xu, Rong Xu, Haoyang Xu, Shanhai Xu, Yinglin Xu, Haoyu Xu, Wenqing Xu, Jiali Xu, Xiaoke Xu, Changliu Xu, Feng-Xia Xu, Carrie Xu, Yuheng Xu, Shimeng Xu, Wanwan Xu, Weiming Xu, Gui-Ping Xu, Zhenzhou Xu, Yangbin Xu, Aohong Xu, Wenlong Xu, Jia-Xin Xu, Luyi Xu, Manyi Xu, De Xu, Changde Xu, Xinxuan Xu, Gaosi Xu, Baofeng Xu, Chang Xu, Wanhai Xu, Qing Xu, Zuyuan Xu, Pingwen Xu, Feng-Yuan Xu, Aoling Xu, Erping Xu, Zhicheng Xu, Shaoqi Xu, Lun-Shan Xu, Shiyao Sherrie Xu, Jianing Xu, Boqing Xu, Janfeng Xu, Yin Xu, Weijie Xu, Yu-Peng Xu, Ya-Nan Xu, Gaoyuan Xu, Iris M J Xu, Zhi Xu, Xiaomeng Xu, Mengyi Xu, Meifang Xu, Houxi Xu, Yuanfeng Xu, Shuqia Xu, Da-Peng Xu, Hong-tao Xu, Yaling Xu, Mei Xu, Xiaojiao Xu, Zhiru Xu, Weide Xu, Dandan Xu, W Xu, Shun Xu, Jianhua Xu, Tongda Xu, Cynthia M Xu, Yechun Xu, Lijun Xu, Xiao-Lin Xu, Ziye Xu, Xiaohan Xu, Guozheng Xu, Rongbin Xu, Nathan Xu, Wangdong Xu, Kailian Xu, Yongfeng Xu, Zhunan Xu, Jiawei Xu, Ruohong Xu, Yuhan Xu, Shanqi Xu, Shoujia Xu, T Xu, Weifeng Xu, Qiuyun Xu, Hu Xu, Yanming Xu, Hongwei Xu, Ziyu Xu, Kaishou Xu, Jian Hua Xu, Xin Xu, Liu Xu, Zetan Xu, Leiting Xu, Yong-Nan Xu, Houguo Xu, Zhizhen Xu, Ya-lin Xu, Xiang Xu, Suowen Xu, Xuejin Xu, Yiming Xu, Shude Xu, Genxing Xu, Yun-Teng Xu, Yanling Xu, Yuanhong Xu, Lijuan Xu, Xingzhi Xu, Guanghao Xu, Qiu-Han Xu, Siqun Xu, Wen-Xiong Xu, Qianghua Xu, Shuangbing Xu, Wenjun Xu, Jiangang Xu, Yangliu Xu, Jinjian Xu, W M Xu, Shanqiang Xu, Zefeng Xu
articles

Interaction of ApoA-IV with NR4A1 and NR1D1 Represses G6Pase and PEPCK Transcription: Nuclear Receptor-Mediated Downregulation of Hepatic Gluconeogenesis in Mice and a Human Hepatocyte Cell Line.

Xiaoming Li, Min Xu, Fei Wang +4 more · 2015 · PloS one · PLOS · added 2026-04-24
We have previously shown that the nuclear receptor, NR1D1, is a cofactor in ApoA-IV-mediated downregulation of gluconeogenesis. Nuclear receptor, NR4A1, is involved in the transcriptional regulation o Show more
We have previously shown that the nuclear receptor, NR1D1, is a cofactor in ApoA-IV-mediated downregulation of gluconeogenesis. Nuclear receptor, NR4A1, is involved in the transcriptional regulation of various genes involved in inflammation, apoptosis, and glucose metabolism. We investigated whether NR4A1 influences the effect of ApoA-IV on hepatic glucose metabolism. Our in situ proximity ligation assays and coimmunoprecipitation experiments indicated that ApoA-IV colocalized with NR4A1 in human liver (HepG2) and kidney (HEK-293) cell lines. The chromatin immunoprecipitation experiments and luciferase reporter assays indicated that the ApoA-IV and NR4A1 colocalized at the RORα response element of the human G6Pase promoter, reducing its transcriptional activity. Our RNA interference experiments showed that knocking down the expression of NR4A1 in primary mouse hepatocytes treated with ApoA-IV increased the expression of NR1D1, G6Pase, and PEPCK, and that knocking down NR1D1 expression increased the level of NR4A1. We also found that ApoA-IV induced the expression of endogenous NR4A1 in both cultured primary mouse hepatocytes and in the mouse liver, and decreased glucose production in primary mouse hepatocytes. Our findings showed that ApoA-IV colocalizes with NR4A1, which suppresses G6Pase and PEPCK gene expression at the transcriptional level, reducing hepatic glucose output and lowering blood glucose. The ApoA-IV-induced increase in NR4A1 expression in hepatocytes mediates further repression of gluconeogenesis. Our findings suggest that NR1D1 and NR4A1 serve similar or complementary functions in the ApoA-IV-mediated regulation of gluconeogenesis. Show less
📄 PDF DOI: 10.1371/journal.pone.0142098
APOA4

The role of apolipoprotein A-IV in regulating glucagon-like peptide-1 secretion.

Fei Wang, Qing Yang, Sarah Huesman +6 more · 2015 · American journal of physiology. Gastrointestinal and liver physiology · added 2026-04-24
Both glucagon-like peptide-1 (GLP-1) and apolipoprotein A-IV (apoA-IV) are produced from the gut and enhance postprandial insulin secretion. This study investigated whether apoA-IV regulates nutrient- Show more
Both glucagon-like peptide-1 (GLP-1) and apolipoprotein A-IV (apoA-IV) are produced from the gut and enhance postprandial insulin secretion. This study investigated whether apoA-IV regulates nutrient-induced GLP-1 secretion and whether apoA-IV knockout causes compensatory GLP-1 release. Using lymph-fistula-mice, we first determined lymphatic GLP-1 secretion by administering apoA-IV before an intraduodenal Ensure infusion. apoA-IV changed neither basal nor Ensure-induced GLP-1 secretion relative to saline administration. We then assessed GLP-1 in apoA-IV-/- and wild-type (WT) mice administered intraduodenal Ensure. apoA-IV-/- mice had comparable lymph flow, lymphatic triglyceride, glucose, and protein outputs as WT mice. Intriguingly, apoA-IV-/- mice had higher lymphatic GLP-1 concentration and output than WT mice 30 min after Ensure administration. Increased GLP-1 was also observed in plasma of apoA-IV-/- mice at 30 min. apoA-IV-/- mice had comparable total gut GLP-1 content relative to WT mice under fasting, but a lower GLP-1 content 30 min after Ensure administration, suggesting that more GLP-1 was secreted. Moreover, an injection of apoA-IV protein did not reverse the increased GLP-1 secretion in apoA-IV-/- mice. Finally, we assessed gene expression of GLUT-2 and the lipid receptors, including G protein-coupled receptor (GPR) 40, GPR119, and GPR120 in intestinal segments. GLUT-2, GPR40 and GPR120 mRNAs were unaltered by apoA-IV knockout. However, ileal GPR119 mRNA was significantly increased in apoA-IV-/- mice. GPR119 colocalizes with GLP-1 in ileum and stimulates GLP-1 secretion by sensing OEA, lysophosphatidylcholine, and 2-monoacylglycerols. We suggest that increased ileal GPR119 is a potential mechanism by which GLP-1 secretion is enhanced in apoA-IV-/- mice. Show less
no PDF DOI: 10.1152/ajpgi.00075.2015
APOA4

TNF-alpha and IL-6 inhibit apolipoprotein A-IV production induced by linoleic acid in human intestinal Caco2 cells.

Xiaoming Li, Min Xu, Min Liu +2 more · 2015 · Journal of inflammation (London, England) · BioMed Central · added 2026-04-24
Apolipoprotein A-IV (apoA-IV) is a protein mainly synthesized by enterocytes in the intestine. Its gene expression is suppressed during fasting and stimulated during active fat absorption. Chronic fee Show more
Apolipoprotein A-IV (apoA-IV) is a protein mainly synthesized by enterocytes in the intestine. Its gene expression is suppressed during fasting and stimulated during active fat absorption. Chronic feeding of a high-fat (HF) diet abolishes the differential expression between fasting and fat-feeding and therefore may contribute to diet-induced obesity since apoA-IV is a potent satiety factor. It is well established that the circulating pro-inflammatory cytokines TNF-α and IL-6 are increased by HF feeding. To determine whether pro-inflammatory cytokines are involved in the diminished response of apoA-IV gene expression to fat-feeding, different concentrations of linoleic acid (LA), an important dietary fatty acid, was used to stimulate apoA-IV expression in human intestinal Caco2 cells. Cells were pre-treated with or without human recombinant TNF-α, IL-6 or their combination before the addition of LA. Real-time PCR and ELISA were used to detect and quantify RNA transcripts and proteins of apoA-IV and the cytokines. LA stimulated gene and protein expression of apoA-IV in a dose and time dependent manner. Pre-treatment with the cytokines for 72 h significantly inhibited the increased expression of apoA-IV gene and protein induced by LA. Furthermore, the cytokines, especially TNF-α, also positively up-regulate the cytokine themselves in Caco2 cells. Our data indicate that the pro-inflammatory cytokines may be responsible for the reduced apoA-IV production in response to fat feeding. Because of apoA-IV's role in satiety, we propose the inhibitory effect of circulating pro-inflammatory cytokines on apoA-IV production contributes to diet-induced obesity. Show less
📄 PDF DOI: 10.1186/s12950-015-0069-0
APOA4

An Association Study Identifies Two Single Nucleotide Polymorphisms on Chromosome 11q23.3 as a Risk Locus for Acute Myocardial Infarction in the Chinese Han Population.

Botao Shen, Wei Zhao, Yang Zheng +3 more · 2015 · Clinical laboratory · added 2026-04-24
To evaluate whether the Chinese Han population harbors genetic markers associated with risk of acute myocardial infarction (MI), which have previously been identified in other ethnic populations. Acco Show more
To evaluate whether the Chinese Han population harbors genetic markers associated with risk of acute myocardial infarction (MI), which have previously been identified in other ethnic populations. According to predefined criteria, 549 Chinese patients with acute MI and 551 Chinese subjects (controls) without a history of coronary artery disease (CAD) were selected for the study. Three prevalent single nucleotide polymorphisms (SNPs; rs1412444(LIPA), rs662799(APOA5) and rs964184(ZNF259)) associated with CAD and MI in other ethnic populations, were selected for sequence and association analyses within blood DNA of the Chinese Han population. Only two SNPs, rs662799 (APOA5) and rs964184 (ZNF259) found at two independent loci, were associated with risk of MI in the Chinese Han population. Using Bonferroni correction methods, significant differences in the association of these two SNPs (rs662799 (p = 0.0228) and rs964184 (p = 0.0060)) between Chinese patients with MI versus controls were revealed. We identified a significant association between two SNPs (rs964184 and rs662799) on chromosome 11q23.3 and MI risk in the Chinese Han population, which extends their clinical relevance to predicting the risk of MI in diverse ethnic populations. Show less
no PDF DOI: 10.7754/clin.lab.2015.150331
APOA5

Positive Association between APOA5 rs662799 Polymorphism and Coronary Heart Disease: A Case-Control Study and Meta-Analysis.

Huadan Ye, Annan Zhou, Qiangxiao Hong +8 more · 2015 · PloS one · PLOS · added 2026-04-24
Apolipoprotein A5 (APOA5) is associated with plasma triglyceride (TG) levels, a risk factor for coronary heart disease (CHD). This study explored the association between CHD and the APOA5 rs662799 pol Show more
Apolipoprotein A5 (APOA5) is associated with plasma triglyceride (TG) levels, a risk factor for coronary heart disease (CHD). This study explored the association between CHD and the APOA5 rs662799 polymorphism. We collected 1,521 samples (783 CHD patients and 738 controls) for this case-control study. Meta-analysis was performed using Review Manager Software and Stata Software. Significant differences were observed between CHD cases and controls at the level of both genotype (χ2 = 8.964, df = 2, P = 0.011) and allele (χ2 = 9.180, df = 1, P = 0.002, OR = 1.275, 95% CI = 1.089-1.492). A breakdown analysis by gender showed a significant association of APOA5 rs662799 with CHD in males (χ2 = 7.770, df = 1, P = 0.005; OR = 1.331, 95% CI = 1.088-1.628). An additional meta-analysis using 21378 cases and 28428 controls established that rs662799 is significantly associated with CHD (P < 0.00001). Both our case-control study and meta-analysis confirm a significant association between APOA5 rs662799 and CHD. In addition, our results suggest a male-specific association between the APOA5 rs662799 polymorphism and CHD. Show less
📄 PDF DOI: 10.1371/journal.pone.0135683
APOA5

Mice lacking prostaglandin E receptor subtype 4 manifest disrupted lipid metabolism attributable to impaired triglyceride clearance.

Yin Cai, Fan Ying, Erfei Song +4 more · 2015 · FASEB journal : official publication of the Federation of American Societies for Experimental Biology · added 2026-04-24
Upon high-fat feeding, prostaglandin E receptor subtype 4 (EP4)-knockout mice gain less body weight than their EP4(+/+) littermates. We investigated the cause of the lean phenotype. The mice showed a Show more
Upon high-fat feeding, prostaglandin E receptor subtype 4 (EP4)-knockout mice gain less body weight than their EP4(+/+) littermates. We investigated the cause of the lean phenotype. The mice showed a 68.8% reduction in weight gain with diminished fat mass that was not attributable to reduced food intake, fat malabsorption, or increased energy expenditure. Plasma triglycerides in the mice were elevated by 244.9%. The increase in plasma triglycerides was independent of changes in hepatic very low density lipoprotein (VLDL)-triglyceride production or intestinal chylomicron-triglyceride synthesis. However, VLDL-triglyceride clearance was drastically impaired in the EP4-knockout mice. The absence of EP4 in mice compromised the activation of lipoprotein lipase (LPL), the key enzyme responsible for trafficking of plasma triglycerides into peripheral tissues. Deficiency in EP4 reduced hepatic mRNA expression of the transcriptional factor cAMP response element binding protein H (by 36.8%) and LPL activators, including apolipoprotein (Apo)a5 (by 40.2%) and Apoc2 (by 61.3%). In summary, the lean phenotype of EP4-deficient mice resulted from reduction in adipose tissue and accretion of other peripheral organs caused by impaired triglyceride clearance. The findings identify a new metabolic dimension in the physiologic role played by endogenous EP4. Show less
no PDF DOI: 10.1096/fj.15-274597
APOA5

Dose apolipoprotein AV has influence on the regulation of fatty acids and triglyceride metabolism in cardiomyocyte in case of obesity.

Jun Luo, Li Xu, Jiang Li +1 more · 2015 · International journal of cardiology · Elsevier · added 2026-04-24
no PDF DOI: 10.1016/j.ijcard.2015.03.119
APOA5

Apolipoprotein A-V deficiency enhances chylomicron production in lymph fistula mice.

Linda S Zhang, Min Xu, Qing Yang +3 more · 2015 · American journal of physiology. Gastrointestinal and liver physiology · added 2026-04-24
Apolipoprotein A-V (apoA-V), a liver-synthesized apolipoprotein discovered in 2001, strongly modulates fasting plasma triglycerides (TG). Little is reported on the effect of apoA-V on postprandial pla Show more
Apolipoprotein A-V (apoA-V), a liver-synthesized apolipoprotein discovered in 2001, strongly modulates fasting plasma triglycerides (TG). Little is reported on the effect of apoA-V on postprandial plasma TG, an independent predictor for atherosclerosis. Overexpressing apoA-V in mice suppresses postprandial TG, but mechanisms focus on increased lipolysis or clearance of remnant particles. Unknown is whether apoA-V suppresses the absorption of dietary lipids by the gut. This study examines how apoA-V deficiency affects the steady-state absorption and lymphatic transport of dietary lipids in chow-fed mice. Using apoA-V knockout (KO, n = 8) and wild-type (WT, n = 8) lymph fistula mice, we analyzed the uptake and lymphatic transport of lipids during a continuous infusion of an emulsion containing [(3)H]triolein and [(14)C]cholesterol. ApoA-V KO mice showed a twofold increase in (3)H (P < 0.001) and a threefold increase in (14)C (P < 0.001) transport into the lymph compared with WT. The increased lymphatic transport was accompanied by a twofold reduction (P < 0.05) in mucosal (3)H, suggesting that apoA-V KO mice more rapidly secreted [(3)H]TG out of the mucosa into the lymph. ApoA-V KO mice also produced chylomicrons more rapidly than WT (P < 0.05), as measured by the transit time of [(14)C]oleic acid from the intestinal lumen to lymph. Interestingly, apoA-V KO mice produced a steadily increasing number of chylomicron particles over time, as measured by lymphatic apoB output. The data suggest that apoA-V suppresses the production of chylomicrons, playing a previously unknown role in lipid metabolism that may contribute to the postprandial hypertriglyceridemia associated with apoA-V deficiency. Show less
no PDF DOI: 10.1152/ajpgi.00339.2014
APOA5

5-hydroxytryptamine receptor (5-HT1DR) promotes colorectal cancer metastasis by regulating Axin1/β-catenin/MMP-7 signaling pathway.

Hua Sui, Hanchen Xu, Qing Ji +9 more · 2015 · Oncotarget · Impact Journals · added 2026-04-24
Overexpression of 5-hydroxytryptamine (5-HT) in human cancer contributes to tumor metastasis, but the role of 5-HT receptor family in cancer has not been thoroughly explored. Here, we report overexpre Show more
Overexpression of 5-hydroxytryptamine (5-HT) in human cancer contributes to tumor metastasis, but the role of 5-HT receptor family in cancer has not been thoroughly explored. Here, we report overexpression of 5-HT(1D) receptor (5-HT(1D)R) was associated with Wnt signaling pathway and advanced tumor stage. The underlying mechanism of 5-HT(1D)R-promoted tumor invasion was through its activation on the Axin1/β-catenin/MMP-7 pathway. In an orthotopic colorectal cancer mouse model, we demonstrated that a 5-HT(1D)R antagonist (GR127935) effectively inhibited tumor metastasis through targeting Axin1. Furthermore, in intestinal epithelium cells, we observed that 5-HT(1D)R played an important role in cell invasion via Axin1/β-catenin/MMP-7 pathway. Together, our findings reveal an essential role of the physiologic level of 5-HT(1D)R in pulmonary metastasis of colorectal cancer. Show less
📄 PDF DOI: 10.18632/oncotarget.4543
AXIN1

BBS4 and BBS5 show functional redundancy in the BBSome to regulate the degradative sorting of ciliary sensory receptors.

Qingwen Xu, Yuxia Zhang, Qing Wei +4 more · 2015 · Scientific reports · Nature · added 2026-04-24
Cilia harbor sensory receptors for various signaling cascades critical for vertebrate development. However, the mechanisms underlying the ciliary homeostasis of sensory receptors remain elusive. Here, Show more
Cilia harbor sensory receptors for various signaling cascades critical for vertebrate development. However, the mechanisms underlying the ciliary homeostasis of sensory receptors remain elusive. Here, we demonstrate that BBS-4 and BBS-5, two distinct BBSome components, show unexpected functional redundancy in the context of cilia in C. elegans. BBS-4 directly interacts with BBS-5 and the interaction can be disrupted by a conserved mutation identified in human BBS4. Surprisingly, we found that BBS-4 and BBS-5 act redundantly in the BBSome to regulate the ciliary removal, rather than the ciliary entry or retrograde IFT transport, of various sensory receptors. Further analyses indicate that co-depletion of BBS-4 and BBS-5 disrupts the lysosome-targeted degradative sorting of ciliary sensory receptors. Moreover, mammalian BBS4 and BBS5 also interact directly and coordinate the ciliary removal of polycystin 2. Hence, we reveal a novel and highly conserved role for the BBSome in fine-tuning ciliary signaling by regulating the ciliary removal of sensory receptors for lysosomal degradation. Show less
📄 PDF DOI: 10.1038/srep11855
BBS4

Excess of rare variants in genes that are key epigenetic regulators of spermatogenesis in the patients with non-obstructive azoospermia.

Zesong Li, Yi Huang, Honggang Li +29 more · 2015 · Scientific reports · Nature · added 2026-04-24
Non-obstructive azoospermia (NOA), a severe form of male infertility, is often suspected to be linked to currently undefined genetic abnormalities. To explore the genetic basis of this condition, we s Show more
Non-obstructive azoospermia (NOA), a severe form of male infertility, is often suspected to be linked to currently undefined genetic abnormalities. To explore the genetic basis of this condition, we successfully sequenced ~650 infertility-related genes in 757 NOA patients and 709 fertile males. We evaluated the contributions of rare variants to the etiology of NOA by identifying individual genes showing nominal associations and testing the genetic burden of a given biological process as a whole. We found a significant excess of rare, non-silent variants in genes that are key epigenetic regulators of spermatogenesis, such as BRWD1, DNMT1, DNMT3B, RNF17, UBR2, USP1 and USP26, in NOA patients (P = 5.5 × 10(-7)), corresponding to a carrier frequency of 22.5% of patients and 13.7% of controls (P = 1.4 × 10(-5)). An accumulation of low-frequency variants was also identified in additional epigenetic genes (BRDT and MTHFR). Our study suggested the potential associations of genetic defects in genes that are epigenetic regulators with spermatogenic failure in human. Show less
📄 PDF DOI: 10.1038/srep08785
BRWD1

Transcription Profiles of Marker Genes Predict The Transdifferentiation Relationship between Eight Types of Liver Cell during Rat Liver Regeneration.

Xiaguang Chen, Cunshuan Xu · 2015 · Cell journal · added 2026-04-24
To investigate the transdifferentiation relationship between eight types of liver cell during rat liver regeneration (LR). 114 healthy Sprague-Dawley (SD) rats were used in this experimental study. Ei Show more
To investigate the transdifferentiation relationship between eight types of liver cell during rat liver regeneration (LR). 114 healthy Sprague-Dawley (SD) rats were used in this experimental study. Eight types of liver cell were isolated and purified with percoll density gradient centrifugation and immunomagentic bead methods. Marker genes for eight types of cell were obtained by retrieving the relevant references and databases. Expression changes of markers for each cell of the eight cell types were measured using microarray. The relationships between the expression profiles of marker genes and transdifferentiation among liver cells were analyzed using bioinformatics. Liver cell transdifferentiation was predicted by comparing expression profiles of marker genes in different liver cells. During LR hepatocytes (HCs) not only express hepatic oval cells (HOC) markers (including PROM1, KRT14 and LY6E), but also express biliary epithelial cell (BEC) markers (including KRT7 and KRT19); BECs express both HOC markers (including GABRP, PCNA and THY1) and HC markers such as CPS1, TAT, KRT8 and KRT18; both HC markers (KRT18, KRT8 and WT1) and BEC markers (KRT7 and KRT19) were detected in HOCs. Additionally, some HC markers were also significantly upregulated in hepatic stellate cells ( HSCs), sinusoidal endothelial cells (SECs) , Kupffer cells (KCs) and dendritic cells (DCs), mainly at 6-72 hours post partial hepatectomy (PH). Our findings indicate that there is a mutual transdifferentiation relationship between HC, BEC and HOC during LR, and a tendency for HSCs, SECs, KCs and DCs to transdifferentiate into HCs. Show less
📄 PDF DOI: 10.22074/cellj.2016.3756
CPS1

A G-quadruplex DNA structure resolvase, RHAU, is essential for spermatogonia differentiation.

X Gao, W Ma, J Nie +11 more · 2015 · Cell death & disease · Nature · added 2026-04-24
G-quadruplex (G4) DNA and G4 DNA resolvase are involved in a variety of biological processes. To understand the biological function of G4 DNA structures and their resolvases in spermatogenesis, we inv Show more
G-quadruplex (G4) DNA and G4 DNA resolvase are involved in a variety of biological processes. To understand the biological function of G4 DNA structures and their resolvases in spermatogenesis, we investigated the distribution of G4 structures in mouse testis and identified their alterations during spermatogenesis. Meanwhile, we studied the function of RNA helicase associated with AU-rich element (RHAU), a G4 DNA resolvase, in spermatogenesis with a germ-cell-specific knockout mouse model. The results showed that the ablation of RHAU in germ cells caused the increase of G4 structures and thus resulted in the decrease of spermatogonial differentiation. c-kit, a spermatogonia differentiation-related gene, contains two G4 DNA motifs on its promoter. We found its expression was significantly downregulated in RHAU conditional knockout testis. A further analysis demonstrated that RHAU directly bound to the G4 structures to activate c-kit expression. We concluded that RHAU regulates spermatogonia differentiation by promoting c-kit expression via directly binding to the G4 DNA motifs c-kit promoter. Show less
📄 PDF DOI: 10.1038/cddis.2014.571
DHX36

The Effect of PSD-93 Deficiency on the Expression of Early Inflammatory Cytokines Induced by Ischemic Brain Injury.

Qingxiu Zhang, Hongyu Cheng, Rong Rong +6 more · 2015 · Cell biochemistry and biophysics · Springer · added 2026-04-24
The aim of the study was to explore the effect of PSD-93 deficiency on the expression of early inflammatory cytokines induced by cerebral ischemia/reperfusion injury. Ten- to twelve-week-old male PSD- Show more
The aim of the study was to explore the effect of PSD-93 deficiency on the expression of early inflammatory cytokines induced by cerebral ischemia/reperfusion injury. Ten- to twelve-week-old male PSD-93 knockout (PSD-93 KO) mice (C57BL/6 genetic background) and wild-type (WT) littermates were randomly divided into sham and ischemia/reperfusion (I/R) group. The focal cerebral I/R model was established by middle cerebral artery occlusion (MCAO) suture method. RT-PCR was used to detect the mRNA expression of IL-6, IL-10, Cox-2, iNOS, and TNF-α4h following reperfusion. Infarct volume at different time points after I/R was analyzed using 2,3,5-triphenyl tetrazolium staining, and neurological damage score (neurological severity scores, NSS) was used to evaluate the effect of PSD-93 gene knockout on the MCAO-induced neurological injury. In WT mice, early I/R injury led to the increase in the mRNA expression of proinflammatory cytokines IL-6, Cox-2, iNOS, and TNF-α that coincided with the decrease in the expression of anti-inflammatory cytokine IL-10, as compared to the sham group (P < 0.05). This effect was markedly attenuated by depleting PSD-93 levels by gene knockout. As compared to sham group, in PSD-93 KO mice I/R4h led to downregulation of Cox-2 and iNOS expression, and increase in the mRNA levels of IL-10 (P < 0.05). In addition, following MCAO, PSD-93 KO mice exhibited improved NSS and reduced infarct volumes, as compared with WT animals. PSD-93 knockout may play a neuroprotective role by mediating the early release of inflammatory cytokines induced by cerebral ischemia. Show less
no PDF DOI: 10.1007/s12013-015-0666-9
DLG2

Genome-wide profiling of HPV integration in cervical cancer identifies clustered genomic hot spots and a potential microhomology-mediated integration mechanism.

Zheng Hu, Da Zhu, Wei Wang +33 more · 2015 · Nature genetics · Nature · added 2026-04-24
Human papillomavirus (HPV) integration is a key genetic event in cervical carcinogenesis. By conducting whole-genome sequencing and high-throughput viral integration detection, we identified 3,667 HPV Show more
Human papillomavirus (HPV) integration is a key genetic event in cervical carcinogenesis. By conducting whole-genome sequencing and high-throughput viral integration detection, we identified 3,667 HPV integration breakpoints in 26 cervical intraepithelial neoplasias, 104 cervical carcinomas and five cell lines. Beyond recalculating frequencies for the previously reported frequent integration sites POU5F1B (9.7%), FHIT (8.7%), KLF12 (7.8%), KLF5 (6.8%), LRP1B (5.8%) and LEPREL1 (4.9%), we discovered new hot spots HMGA2 (7.8%), DLG2 (4.9%) and SEMA3D (4.9%). Protein expression from FHIT and LRP1B was downregulated when HPV integrated in their introns. Protein expression from MYC and HMGA2 was elevated when HPV integrated into flanking regions. Moreover, microhomologous sequence between the human and HPV genomes was significantly enriched near integration breakpoints, indicating that fusion between viral and human DNA may have occurred by microhomology-mediated DNA repair pathways. Our data provide insights into HPV integration-driven cervical carcinogenesis. Show less
no PDF DOI: 10.1038/ng.3178
DLG2

Silencing of DUSP6 gene by RNAi-mediation inhibits proliferation and growth in MDA-MB-231 breast cancer cells: an in vitro study.

Hongming Song, Chenyang Wu, Chuankui Wei +6 more · 2015 · International journal of clinical and experimental medicine · added 2026-04-24
Dual-specificity phosphatase 6 (DUSP6) is a negative feedback mechanism of the mitogen-activated protein (MAP) kinase superfamily (MAPK/ERK, SAPK/JNK, p38), that is associated with cellular proliferat Show more
Dual-specificity phosphatase 6 (DUSP6) is a negative feedback mechanism of the mitogen-activated protein (MAP) kinase superfamily (MAPK/ERK, SAPK/JNK, p38), that is associated with cellular proliferation and differentiation. It has been reported that the expression of DUSP6 in different types of breast cancer is diverse and therefore it has altered functions in various types of breast cancer. Our aim was to explore the exact function of DUSP6 in triple-negative breast cancer cells (MDA-MB-231 cell) and to determine whether the suppression of DUSP6 by small interfering RNA (siRNA) and mircroRNA (miRNA) inhibits the growth of human MDA-MB-231 breast cancer cells. DUSP6-siRNA was used to inhibit the expression of DUSP6 directly and miR-145 to inhibit the expression of DUSP6 either in MDA-MB-231 breast cancer cells and successful transfection being confirmed by Real-time PCR and Western Blotting. Down regulation of DUSP6 in MDA-MB-231 cells suppressed the cell proliferation as investigated by MTT assay and colony form assay. Transwell test and Scratch assay were conducted to investigate the migration and invasion of MDA-MB-231 cells. T-test (two-tailed) was used to compare differences between groups, and the significance level was set at P<0.05. DUSP6 mRNA expression and protein expression were reduced after transfection with DUSP6-siRNA directly and similar trend with transfection with miR-145. The treated group with DUSP6-siRNA or miR-145 suppressed MDA-MB-231 cells proliferation, migration and invasion, and meanwhile the cells were arrested at G0/G1 phase. DUSP6 plays a role in triple-negative breast cancer cells that might promote growth in MDA-MB-231 triple-negative breast cancer cells. Show less
no PDF
DUSP6

Identification and characterization of NF-kappaB binding sites in human miR-1908 promoter.

Qianhuining Kuang, Jingyun Li, Lianghui You +5 more · 2015 · Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · Elsevier · added 2026-04-24
Previous studies reported that miR-1908 was highly expressed in mature human adipocytes. Adipokines tumor necrosis factor α (TNF-α) that was known to activate NF-kappaB signaling could affect the expr Show more
Previous studies reported that miR-1908 was highly expressed in mature human adipocytes. Adipokines tumor necrosis factor α (TNF-α) that was known to activate NF-kappaB signaling could affect the expression of miR-1908 in adipocytes. However, little is known about the underlying mechanisms. In this study, we identified miR-1908 promoter using polymerase chain reaction (PCR) from human genomic DNA. Bioinformatic analysis was applied to predict the NF-kappaB binding sites in miR-1908 promoter. Real-time PCR, dual luciferase reporter assay, Mutagenesis analysis and electrophoretic mobility shift assay (EMSA) were performed to demonstrate the function of NF-kappaB binding sites in miR-1908 promoter. 1243bp miR-1908 promoter located in the intron of host gene fatty acid desaturase 1 (FADS1). Bioinformatic analysis revealed the presence of two putative NF-kappaB binding sites. TNF-α restricts miR-1908 expression in preadipocytes, and TNF-α decreases miR-1908 promoter activity in HEK293T cells. In addition, those two NF-kappaB transcription factor binding sites in miR-1908 promoter were functional. Our findings demonstrated that miR-1908 has its own transcription unit, and revealed the transcriptional mechanisms of miR-1908 expression based on NF-kappaB signaling. This study offers a theoretical basis for understanding the transcriptional mechanism of miR-1908 expression and may provide a new strategy for obesity clinical therapy. Show less
no PDF DOI: 10.1016/j.biopha.2015.08.018
FADS1

Effects of metformin on metabolite profiles and LDL cholesterol in patients with type 2 diabetes.

Tao Xu, Stefan Brandmaier, Ana C Messias +45 more · 2015 · Diabetes care · added 2026-04-24
Metformin is used as a first-line oral treatment for type 2 diabetes (T2D). However, the underlying mechanism is not fully understood. Here, we aimed to comprehensively investigate the pleiotropic eff Show more
Metformin is used as a first-line oral treatment for type 2 diabetes (T2D). However, the underlying mechanism is not fully understood. Here, we aimed to comprehensively investigate the pleiotropic effects of metformin. We analyzed both metabolomic and genomic data of the population-based KORA cohort. To evaluate the effect of metformin treatment on metabolite concentrations, we quantified 131 metabolites in fasting serum samples and used multivariable linear regression models in three independent cross-sectional studies (n = 151 patients with T2D treated with metformin [mt-T2D]). Additionally, we used linear mixed-effect models to study the longitudinal KORA samples (n = 912) and performed mediation analyses to investigate the effects of metformin intake on blood lipid profiles. We combined genotyping data with the identified metformin-associated metabolites in KORA individuals (n = 1,809) and explored the underlying pathways. We found significantly lower (P < 5.0E-06) concentrations of three metabolites (acyl-alkyl phosphatidylcholines [PCs]) when comparing mt-T2D with four control groups who were not using glucose-lowering oral medication. These findings were controlled for conventional risk factors of T2D and replicated in two independent studies. Furthermore, we observed that the levels of these metabolites decreased significantly in patients after they started metformin treatment during 7 years' follow-up. The reduction of these metabolites was also associated with a lowered blood level of LDL cholesterol (LDL-C). Variations of these three metabolites were significantly associated with 17 genes (including FADS1 and FADS2) and controlled by AMPK, a metformin target. Our results indicate that metformin intake activates AMPK and consequently suppresses FADS, which leads to reduced levels of the three acyl-alkyl PCs and LDL-C. Our findings suggest potential beneficial effects of metformin in the prevention of cardiovascular disease. Show less
no PDF DOI: 10.2337/dc15-0658
FADS1

Alterations of a Cellular Cholesterol Metabolism Network Are a Molecular Feature of Obesity-Related Type 2 Diabetes and Cardiovascular Disease.

Jingzhong Ding, Lindsay M Reynolds, Tanja Zeller +26 more · 2015 · Diabetes · added 2026-04-24
Obesity is linked to type 2 diabetes (T2D) and cardiovascular diseases; however, the underlying molecular mechanisms remain unclear. We aimed to identify obesity-associated molecular features that may Show more
Obesity is linked to type 2 diabetes (T2D) and cardiovascular diseases; however, the underlying molecular mechanisms remain unclear. We aimed to identify obesity-associated molecular features that may contribute to obesity-related diseases. Using circulating monocytes from 1,264 Multi-Ethnic Study of Atherosclerosis (MESA) participants, we quantified the transcriptome and epigenome. We discovered that alterations in a network of coexpressed cholesterol metabolism genes are a signature feature of obesity and inflammatory stress. This network included 11 BMI-associated genes related to sterol uptake (↑LDLR, ↓MYLIP), synthesis (↑SCD, FADS1, HMGCS1, FDFT1, SQLE, CYP51A1, SC4MOL), and efflux (↓ABCA1, ABCG1), producing a molecular profile expected to increase intracellular cholesterol. Importantly, these alterations were associated with T2D and coronary artery calcium (CAC), independent from cardiometabolic factors, including serum lipid profiles. This network mediated the associations between obesity and T2D/CAC. Several genes in the network harbored C-phosphorus-G dinucleotides (e.g., ABCG1/cg06500161), which overlapped Encyclopedia of DNA Elements (ENCODE)-annotated regulatory regions and had methylation profiles that mediated the associations between BMI/inflammation and expression of their cognate genes. Taken together with several lines of previous experimental evidence, these data suggest that alterations of the cholesterol metabolism gene network represent a molecular link between obesity/inflammation and T2D/CAC. Show less
no PDF DOI: 10.2337/db14-1314
FADS1

Qingyihuaji Formula Inhibits Pancreatic Cancer and Prolongs Survival by Downregulating Hes-1 and Hey-1.

Yanli Xu, Shan Xu, Yueqin Cai +1 more · 2015 · Evidence-based complementary and alternative medicine : eCAM · added 2026-04-24
The dire prognosis of pancreatic cancer has not markedly improved during past decades. The present study was carried out to explore the effect of Qingyihuaji formula (QYHJ) on inhibiting pancreatic ca Show more
The dire prognosis of pancreatic cancer has not markedly improved during past decades. The present study was carried out to explore the effect of Qingyihuaji formula (QYHJ) on inhibiting pancreatic cancer and prolonging survival in related Notch signaling pathway. Proliferation of pancreatic cancer cells (SW1990 and PANC-1) was detected by MTT assay at 24, 48, and 72 h with exposure to various concentrations (0.08-50 mg/mL) of QYHJ water extract. Pancreatic tumor models of nude mice were divided into three groups randomly (control, QYHJ, and gemcitabine). mRNA and protein expression of Notch target genes (Hes-1, Hey-1, Hey-2, and Hey-L) in dissected tumor tissue were detected. Results showed that proliferation of SW1990 cells and PANC-1 cells was inhibited by QYHJ water extract in a dose-dependent and time-dependent manner. QYHJ effectively inhibited tumor growth and prolonged survival time in nude mice. Expression of both Hes-1 and Hey-1 was decreased significantly in QYHJ group, suggesting that Hes-1 and Hey-1 in Notch signaling pathway might be potential targets for QYHJ treatment. This research could help explain the clinical effectiveness of QYHJ and may provide advanced pancreatic cancer patients with a new therapeutic option. Show less
📄 PDF DOI: 10.1155/2015/145016
HEY2

Myofibroblastic transformation of rat hepatic stellate cells: the role of Notch signaling and epithelial-mesenchymal transition regulation.

Q-D Zhang, M-Y Xu, X-B Cai +3 more · 2015 · European review for medical and pharmacological sciences · added 2026-04-24
The development of liver fibrosis has been shown to be associated with the transition of quiescent hepatic stellate cells (HSCs) into myofibroblastic HSCs, and the Notch signaling system has been show Show more
The development of liver fibrosis has been shown to be associated with the transition of quiescent hepatic stellate cells (HSCs) into myofibroblastic HSCs, and the Notch signaling system has been shown to be activated in this process. The Notch signaling pathway is also known to regulate epithelial-mesenchymal transition (EMT). In the current study, quiescent HSCs were examined for expression of EMT markers, and experiments were performed to determine whether these markers change as quiescent HSCs transition into myofibroblastic HSCs and whether the process is modulated by Notch signaling. To promote myofibroblastic transition under experimental conditions, enzymatic perfusion and density gradient centrifugation were used to isolate rat HSCs, which were then cultured. A γ-secretase inhibitor was used to inhibit Notch signaling pathway activity in primary rat HSCs. Upregulated expression of myofibroblastic markers was observed, but expression of quiescent HSC markers and epithelial markers was downregulated during the transition of HSC in vitro. Data indicate that expression of the classical EMT marker; i.e., E-cadherin, was decreased and that of N-cadherin and snail 1 increased. Notch 2 and Notch 3 receptors and Hey2 and HeyL target genes expression increased significantly as quiescent HSCs transitioned into myofibroblastic HSCs. When Notch signaling was blocked, however, the myofibroblastic transition of HSCs reverted, and epithelial marker expression was restored. Thus, targeting Notch signaling may provide new insights into the mechanism of HSC transition and may offer a possible therapeutic target for the treatment of hepatic injury. Show less
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HEY2

Expression pattern of JMJD1C in oocytes and its impact on early embryonic development.

C H Li, Y Gao, S Wang +7 more · 2015 · Genetics and molecular research : GMR · added 2026-04-24
Cell reprogramming mediated by histone methylation and demethylation is crucial for the activation of the embryonic genome in early embryonic development. In this study, we employed quantitative real- Show more
Cell reprogramming mediated by histone methylation and demethylation is crucial for the activation of the embryonic genome in early embryonic development. In this study, we employed quantitative real-time polymerase chain reaction (qRT-PCR) to detect mRNA levels and expression patterns of all known histone demethylases in early germinal vesicle stage and in vitro-matured metaphase II (MII) oocytes (which are commonly used as donor cells for nuclear transfer). On screening, the Jumonji domain containing 1C (JMJD1C) gene had the highest level of expression and hence was used for subsequent experiments. We also found that JMJD1C was primarily expressed in the nucleus and showed relatively high levels of expression at the 2-cell, 4-cell, 8-cell, 16-cell, morula, and blastocyst stages of embryos developed from MII oocytes fertilized in vitro. Further, we knocked down the JMJD1C gene in MII oocytes using siRNA and monitored the cleavage of zygotes and development of early embryos after in vitro fertilization. The results showed that the zygote cleavage and blastocyst rates of the transfection group were reduced by 57.1 ± 0.07 and 50 ± 0.01% respectively, which were significantly lower than those of the negative control group (P < 0.05). These data suggest that JMJD1C plays a key role in the normal development of early bovine embryos. Our results also provide a theoretical basis for the investigation of the role and molecular mechanism of histone demethylation in the early development of bovine embryos. Show less
no PDF DOI: 10.4238/2015.December.23.12
JMJD1C

LINGO-1 antibody ameliorates myelin impairment and spatial memory deficits in experimental autoimmune encephalomyelitis mice.

Jun-Jun Sun, Qing-Guo Ren, Lin Xu +1 more · 2015 · Scientific reports · Nature · added 2026-04-24
More than 50% of multiple sclerosis patients develop cognitive impairment. However, the underlying mechanisms are still unclear, and there is no effective treatment. LINGO-1 (LRR and Ig domain contain Show more
More than 50% of multiple sclerosis patients develop cognitive impairment. However, the underlying mechanisms are still unclear, and there is no effective treatment. LINGO-1 (LRR and Ig domain containing NOGO receptor interacting protein 1) has been identified as an inhibitor of oligodendrocyte differentiation and myelination. Using the experimental autoimmune encephalomyelitis (EAE) mouse model, we assessed cognitive function at early and late stages of EAE, determined brain expression of myelin basic protein (MBP) and investigated whether the LINGO-1 antibody could restore deficits in learning and memory and ameliorate any loss of MBP. We found that deficits in learning and memory occurred in late EAE and identified decreased expression of MBP in the parahippocampal cortex (PHC) and fimbria-fornix. Moreover, the LINGO-1 antibody significantly improved learning and memory in EAE and partially restored MBP in PHC. Furthermore, the LINGO-1 antibody activated the AKT/mTOR signaling pathway regulating myelin growth. Our results suggest that demyelination in the PHC and fimbria-fornix might contribute to cognitive deficits and the LINGO-1 antibody could ameliorate these deficits by promoting myelin growth in the PHC. Our research demonstrates that LINGO-1 antagonism may be an effective approach to the treatment of the cognitive impairment of multiple sclerosis patients. Show less
📄 PDF DOI: 10.1038/srep14235
LINGO1

LRIG1 extracellular domain: structure and function analysis.

Yibin Xu, Priscilla Soo, Francesca Walker +8 more · 2015 · Journal of molecular biology · Elsevier · added 2026-04-24
We have expressed and purified three soluble fragments of the human LRIG1-ECD (extracellular domain): the LRIG1-LRR (leucine-rich repeat) domain, the LRIG1-3Ig (immunoglobulin-like) domain, and the LR Show more
We have expressed and purified three soluble fragments of the human LRIG1-ECD (extracellular domain): the LRIG1-LRR (leucine-rich repeat) domain, the LRIG1-3Ig (immunoglobulin-like) domain, and the LRIG1-LRR-1Ig fragment using baculovirus vectors in insect cells. The two LRIG1 domains crystallised so that we have been able to determine the three-dimensional structures at 2.3Å resolution. We developed a three-dimensional structure for the LRIG1-ECD using homology modelling based on the LINGO-1 structure. The LRIG1-LRR domain and the LRIG1-LRR-1Ig fragment are monomers in solution, whereas the LRIG1-3Ig domain appears to be dimeric. We could not detect any binding of the LRIG1 domains or the LRIG1-LRR-1Ig fragment to the EGF receptor (EGFR), either in solution using biosensor analysis or when the EGFR was expressed on the cell surface. The FLAG-tagged LRIG1-LRR-1Ig fragment binds weakly to colon cancer cells regardless of the presence of EGFRs. Similarly, neither the soluble LRIG1-LRR nor the LRIG1-3Ig domains nor the full-length LRIG1 co-expressed in HEK293 cells inhibited ligand-stimulated activation of cell-surface EGFR. Show less
no PDF DOI: 10.1016/j.jmb.2015.03.001
LINGO1

WNK1 is involved in Nogo66 inhibition of OPC differentiation.

Zhao-Huan Zhang, Jiao-Jiao Li, Qing-Jin Wang +4 more · 2015 · Molecular and cellular neurosciences · Elsevier · added 2026-04-24
LINGO-1 is a transmembrane receptor expressed primarily in the central nervous system (CNS) and plays an important role in myelination. Recent studies have indicated that it is also involved in oligod Show more
LINGO-1 is a transmembrane receptor expressed primarily in the central nervous system (CNS) and plays an important role in myelination. Recent studies have indicated that it is also involved in oligodendrocyte precursor cell (OPC) survival and differentiation; however, the downstream signaling pathway underlying OPC development is unknown. In our previous study, we found that LINGO-1 is associated with WNK1 in mediating Nogo-induced neurite extension inhibition by RhoA activation. In an effort to identify the role of LINGO-1-WNK1 in OPCs, we first confirmed that WNK1 is also expressed in OPCs and co-localized with LINGO-1, which suppresses WNK1 expression by RNA interference-attenuated Nogo66-induced inhibition of OPC differentiation. Furthermore, we mapped the WNK1 kinase domain using several fragmented peptides to identify the key region of interaction with LINGO-1. We found that a sequence corresponding to the D6 peptide is necessary for the interaction. Finally, we found that using the TAT-D6 peptide to introduce D6 peptide into primary cultured OPC inhibits the association between LINGO-1 and WNK1 and significantly attenuates Nogo66-induced inhibition of OPC differentiation. Taken together, our results show that WNK1, via a specific region on WNK1 kinase domain, interacts with LINGO-1, thus mediating Nogo66-inhibited OPC differentiation. Show less
no PDF DOI: 10.1016/j.mcn.2015.03.003
LINGO1

The glucose-sensing transcription factor MLX promotes myogenesis via myokine signaling.

Liam C Hunt, Beisi Xu, David Finkelstein +5 more · 2015 · Genes & development · Cold Spring Harbor Laboratory · added 2026-04-24
Metabolic stress and changes in nutrient levels modulate many aspects of skeletal muscle function during aging and disease. Growth factors and cytokines secreted by skeletal muscle, known as myokines, Show more
Metabolic stress and changes in nutrient levels modulate many aspects of skeletal muscle function during aging and disease. Growth factors and cytokines secreted by skeletal muscle, known as myokines, are important signaling factors, but it is largely unknown whether they modulate muscle growth and differentiation in response to nutrients. Here, we found that changes in glucose levels increase the activity of the glucose-responsive transcription factor MLX (Max-like protein X), which promotes and is necessary for myoblast fusion. MLX promotes myogenesis not via an adjustment of glucose metabolism but rather by inducing the expression of several myokines, including insulin-like growth factor 2 (IGF2), whereas RNAi and dominant-negative MLX reduce IGF2 expression and block myogenesis. This phenotype is rescued by conditioned medium from control muscle cells and by recombinant IGF2, which activates the myogenic kinase Akt. Importantly, MLX-null mice display decreased IGF2 induction and diminished muscle regeneration in response to injury, indicating that the myogenic function of MLX is manifested in vivo. Thus, glucose is a signaling molecule that regulates myogenesis and muscle regeneration via MLX/IGF2/Akt signaling. Show less
📄 PDF DOI: 10.1101/gad.267419.115
MLXIPL

Dietary fiber prevents obesity-related liver lipotoxicity by modulating sterol-regulatory element binding protein pathway in C57BL/6J mice fed a high-fat/cholesterol diet.

Shufen Han, Jun Jiao, Wei Zhang +5 more · 2015 · Scientific reports · Nature · added 2026-04-24
Adequate intake of dietary fibers has proven metabolic and cardiovascular benefits, molecular mechanisms remain still limited. This study was aimed to investigate the effects of cereal dietary fiber o Show more
Adequate intake of dietary fibers has proven metabolic and cardiovascular benefits, molecular mechanisms remain still limited. This study was aimed to investigate the effects of cereal dietary fiber on obesity-related liver lipotoxicity in C57BL/6J mice fed a high-fat/cholesterol (HFC) diet and underlying mechanism. Forty-eight adult male C57BL/6J mice were randomly given a reference chow diet, or a high fat/cholesterol (HFC) diet supplemented with or without oat fiber or wheat bran fiber for 24 weeks. Our results showed mice fed oat or wheat bran fiber exhibited lower weight gain, lipid profiles and insulin resistance, compared with HFC diet. The two cereal dietary fibers potently decreased protein expressions of sterol regulatory element binding protein-1 and key factors involved in lipogenesis, including fatty acid synthase and acetyl-CoA carboxylase in target tissues. At molecular level, the two cereal dietary fibers augmented protein expressions of peroxisome proliferator-activated receptor alpha and gamma, liver X receptor alpha, and ATP-binding cassette transporter A1 in target tissues. Our findings indicated that cereal dietary fiber supplementation abrogated obesity-related liver lipotoxicity and dyslipidemia in C57BL/6J mice fed a HFC diet. In addition, the efficacy of oat fiber is greater than wheat bran fiber in normalizing these metabolic disorders and pathological profiles. Show less
no PDF DOI: 10.1038/srep15256
NR1H3

Predicting selective liver X receptor β agonists using multiple machine learning methods.

Yali Li, Ling Wang, Zhihong Liu +4 more · 2015 · Molecular bioSystems · Royal Society of Chemistry · added 2026-04-24
Liver X receptor (LXR) α and β are cholesterol sensors; they respond to excess cholesterol and stimulate reverse cholesterol transport. Activating LXRs represents a promising therapeutic option for dy Show more
Liver X receptor (LXR) α and β are cholesterol sensors; they respond to excess cholesterol and stimulate reverse cholesterol transport. Activating LXRs represents a promising therapeutic option for dyslipidemia. However, activating LXRα may cause unwanted lipogenicity. A better anti-dyslipidemia strategy would be to develop selective LXRβ agonists that do not activate LXRα. In this paper, a data set of 234 selective and non-selective LXRβ agonists was collected from the literature. For the first time, we derived the classification models from the data set to predict selective LXRβ agonists using multiple machine learning methods (naïve Bayesian (NB), Recursive Partitioning (RP), Support Vector Machine (SVM), and k-Nearest Neighbors (kNN) methods) with optimized property descriptors and structural fingerprints. The models were optimized from 324 multiple machine learning models, and most of the models showed high predictive abilities (overall predictive accuracies of >80%) for both training and test sets. The top 15 models were evaluated using an external test set of 76 compounds (all containing new scaffolds), and 10 of them displayed overall predictive accuracies exceeding 90%. The top models can be used for the virtual screening of selective LXRβ agonists. The NB models can identify privileged and unprivileged fragments for selective LXRβ agonists, and the fragments can be used to guide the design of new selective LXRβ agonists. Show less
no PDF DOI: 10.1039/c4mb00718b
NR1H3

Divergent roles of BECN1 in LC3 lipidation and autophagosomal function.

Ruina He, Jingyu Peng, Pengfei Yuan +2 more · 2015 · Autophagy · Taylor & Francis · added 2026-04-24
BECN1/Beclin 1 is regarded as a critical component in the class III phosphatidylinositol 3-kinase (PtdIns3K) complex to trigger autophagy in mammalian cells. Despite its significant role in a number o Show more
BECN1/Beclin 1 is regarded as a critical component in the class III phosphatidylinositol 3-kinase (PtdIns3K) complex to trigger autophagy in mammalian cells. Despite its significant role in a number of cellular and physiological processes, the exact function of BECN1 in autophagy remains controversial. Here we created a BECN1 knockout human cell line using the TALEN technique. Surprisingly, the complete loss of BECN1 had little effect on LC3 (MAP1LC3B/LC3B) lipidation, and LC3B puncta resembling autophagosomes by fluorescence microscopy were still evident albeit significantly smaller than those in the wild-type cells. Electron microscopy (EM) analysis revealed that BECN1 deficiency led to malformed autophagosome-like structures containing multiple layers of membranes under amino acid starvation. We further confirmed that the PtdIns3K complex activity and autophagy flux were disrupted in BECN1(-/-) cells. Our results demonstrate the essential role of BECN1 in the functional formation of autophagosomes, but not in LC3B lipidation. Show less
no PDF DOI: 10.1080/15548627.2015.1034404
PIK3C3

Modification of BECN1 by ISG15 plays a crucial role in autophagy regulation by type I IFN/interferon.

Daichao Xu, Tao Zhang, Juan Xiao +6 more · 2015 · Autophagy · Taylor & Francis · added 2026-04-24
ISG15 (ISG15 ubiquitin-like modifier), a ubiquitin-like protein, is one of the major type I IFN (interferon) effector systems. ISG15 can be conjugated to target proteins (ISGylation) via the stepwise Show more
ISG15 (ISG15 ubiquitin-like modifier), a ubiquitin-like protein, is one of the major type I IFN (interferon) effector systems. ISG15 can be conjugated to target proteins (ISGylation) via the stepwise action of E1, E2, and E3 enzymes. Conjugated ISG15 can be removed (deISGylated) from target proteins by USP18 (ubiquitin-specific peptidase 18). Here we investigated the role of deISGylation by USP18 in regulating autophagy and EGFR degradation in cells treated with type I IFNs. We show that type I IFN induced expression of ISG15 leads to ISGylation of BECN1 at Lys117, as well as Lys263, Lys265, and Lys266 which competes with Lys63 ubiquitination of BECN1. We demonstrate that ISGylation of BECN1 at Lys117, as well as Lys263, Lys265, and Lys266 serve an important role in negative regulation of intracellular processes including autophagy and EGFR degradation that are critically dependent upon the activity of class III PtdIns 3-kinase. Our studies provide fundamental new mechanistic insights into the innate immunity response implemented by type I IFNs. Show less
no PDF DOI: 10.1080/15548627.2015.1023982
PIK3C3