Rabbits are well-domesticated animals. As a crucial economic animal, rabbit has been successfully bred into wool-use, meat-use and fur-use breeds. Hair length is one of the most economically important Show more
Rabbits are well-domesticated animals. As a crucial economic animal, rabbit has been successfully bred into wool-use, meat-use and fur-use breeds. Hair length is one of the most economically important traits affecting profitability in wool rabbits. In this study, to identify selection signatures with the long-hair trait, whole-genomic resequencing of long-haired rabbits (Angora rabbits) and short-haired rabbits (Rex and New Zealand rabbits) was performed. By genome-wide selective sweeping analysis based on population comparison, we identified a total of 5.85 Mb regions (containing 174 candidate genes) with strong selection signals. Six of these genes (Dusp1, Ihh, Fam134a, Map3k1, Spata16, and Fgf5) were enriched in the MAPK signalling and Hedgehog signalling pathways, both of which are closely associated with hair growth regulation. Among these genes, Fgf5 encodes the FGF5 protein, which is a well-established regulator of hair growth. There was a nonsynonymous nucleotide substitution (T19234C) in the Fgf5 gene. At this locus, the C allele was present in all of the tested Angora rabbits, while the T allele was dominant in New Zealand and Rex rabbits. We further confirmed that the C allele was conserved in Angora rabbits by screening an additional 135 rabbits. Moreover, the results of functional predictions and co-immunoprecipitation revealed that the T19234C mutation impaired the binding capacity of FGF5 to its receptor FGFR1. We discovered that the homozygous missense mutation T19234C within Fgf5 might contribute to the long-hair trait of Angora rabbits by reducing its receptor binding capacity. This finding will provide new insights into the genetic basis underlying the genetic improvement of Angora rabbits and benefit the improvement of rabbit breeding in the future. Show less
Ufmylation is a recently identified small ubiquitin-like modification, whose biological function and relevant cellular targets are poorly understood. Here we present evidence of a neuroprotective role Show more
Ufmylation is a recently identified small ubiquitin-like modification, whose biological function and relevant cellular targets are poorly understood. Here we present evidence of a neuroprotective role for Ufmylation involving Autophagy-related gene 9 (Atg9) during Drosophila aging. The Ufm1 system ensures the health of aged neurons via Atg9 by coordinating autophagy and mTORC1, and maintaining mitochondrial homeostasis and JNK (c-Jun N-terminal kinase) activity. Neuron-specific expression of Atg9 suppresses the age-associated movement defect and lethality caused by loss of Ufmylation. Furthermore, Atg9 is identified as a conserved target of Ufm1 conjugation mediated by Ddrgk1, a critical regulator of Ufmylation. Mammalian Ddrgk1 was shown to be indispensable for the stability of endogenous Atg9A protein in mouse embryonic fibroblast (MEF) cells. Taken together, our findings might have important implications for neurodegenerative diseases in mammals. Show less
Prostate cancer is the most common malignant tumor of male urogenital system that occurs in prostate epithelium. However, relationship between CAV1 and KRT5 and prostate cancer remains unclear. The pr Show more
Prostate cancer is the most common malignant tumor of male urogenital system that occurs in prostate epithelium. However, relationship between CAV1 and KRT5 and prostate cancer remains unclear. The prostate cancer datasets GSE114740 and GSE200879 were downloaded from Gene Expression Omnibus generated by GPL11154 and GPL32170. De-batch processing was performed, differentially expressed genes (DEGs) were screened, and weighted gene co-expression network analysis. The construction and analysis of protein-protein interaction network, functional enrichment analysis, gene set enrichment analysis. Gene expression heat map was drawn and immune infiltration analysis was performed. Comparative toxicogenomics database analysis were performed to find the disease most related to core gene. In addition, the cell experiment was performed to verify the role of CAV1 and KRT5 by western blot. Divided into 4 groups: control, prostate cancer, prostate cancer-over expression, and prostate cancer- knock out. TargetScan screened miRNAs that regulated central DEGs; 770 DEGs were identified. According to Gene Ontology analysis, they were mainly concentrated in actin binding and G protein coupled receptor binding. In Kyoto Encyclopedia of Gene and Genome analysis, they were mainly concentrated in PI3K-Akt signal pathway, MAPK signal pathway, and ErbB signal pathway. The intersection of enrichment terms of differentially expressed genes and GOKEGG enrichment terms was mainly concentrated in ErbB signaling pathway and MAPK signaling pathway. Three important modules were generated. The protein-protein interaction network obtained 8 core genes (CAV1, BDNF, TGFB3, FGFR1, PRKCA, DLG4, SNAI2, KRT5). Heat map of gene expression showed that core genes (CAV1, TGFB3, FGFR1, SNAI2, KRT5) are highly expressed in prostate cancer tissues and low in normal tissues. Comparative toxicogenomics database analysis showed that core genes (CAV1, TGFB3, FGFR1, SNAI2, KRT5) were associated with prostate tumor, cancer, tumor metastasis, necrosis, and inflammation. CAV1 and KRT5 are up-regulated in prostate cancer. CAV1 and KRT5 are highly expressed in prostate cancer. The higher expression of CAV1 and KRT5, the worse prognosis. Show less
Hypoxia contributes to tumor progression and confers drug resistance. We attempted to microdissect the hypoxia landscape in colon cancer (CC) and explore its correlation with immunotherapy response. T Show more
Hypoxia contributes to tumor progression and confers drug resistance. We attempted to microdissect the hypoxia landscape in colon cancer (CC) and explore its correlation with immunotherapy response. The hypoxia landscape in CC patients was microdissected through unsupervised clustering. The "xCell" algorithms were applied to decipher the tumor immune infiltration characteristics. A hypoxia-related index signature was developed via the LASSO (least absolute shrinkage and selection operator) Cox regression in The Cancer Genome Atlas (TCGA)-colon adenocarcinoma (COAD) cohort and validated in an independent dataset from the Gene Expression Omnibus (GEO) database. The tumor immune dysfunction and exclusion (TIDE) algorithm was utilized to evaluate the correlation between the hypoxia-related index (HRI) signature and immunotherapy response. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blotting were performed to verify the mRNA expression levels of five key genes. The Cell Counting Kit-8 (CCK-8) assay and flow cytometry were performed to examine the cell viability and cell apoptosis. Patients were classified into hypoxia-high, hypoxia-median, and hypoxia-low clusters in TCGA-COAD and verified in the GSE 17538 dataset. Compared with the hypoxia-low cluster, the hypoxia-high cluster consistently presented an unfavorable prognosis, higher immune scores, and stromal scores and elevated infiltration levels of several critical immune and stromal cells. Otherwise, we also found 600 hypoxia-related differentially expressed genes (HRDEGs) between the hypoxia-high cluster and the hypoxia-low cluster. Based on the 600 HRDEGs, we constructed the HRI signature which consists of 11 genes and shows a good prognostic value in both TCGA-COAD and GSE 17538 (AUC of 6-year survival prediction >0.75). Patients with low HRI scores were consistently predicted to be more responsive to immunotherapy. Of the 11 HRI signature genes, RGS16, SNAI1, CDR2L, FRMD5, and FSTL3 were differently expressed between tumors and adjacent tissues. Low expression of SNAI1, CDR2L, FRMD5, and FSTL3 could induce cell viability and promote tumor cell apoptosis. In our study, we discovered three hypoxia clusters which correlate with the clinical outcome and the tumor immune microenvironment in CC. Based on the hypoxia cluster and HRDEGs, we constructed a reliable HRI signature that could accurately predict the prognosis and immunotherapeutic responsiveness in CC patients and discovered four key genes that could affect tumor cell viability and apoptosis. Show less
The pathogenic mechanism of dilated cardiomyopathy (DCM) remains to be defined. This study aimed to identify hub genes and immune cells that could serve as potential therapeutic targets for DCM. We do Show more
The pathogenic mechanism of dilated cardiomyopathy (DCM) remains to be defined. This study aimed to identify hub genes and immune cells that could serve as potential therapeutic targets for DCM. We downloaded four datasets from the Gene Expression Omnibus (GEO) database: GSE141910, GSE3585, GSE42955 and GSE79962. Weighted gene coexpression network analysis (WGCNA) and differential expression analysis were performed to identify gene panels related to DCM. Meanwhile, the CIBERSORT algorithm was used to estimate the immune cells in DCM tissues. Multiple machine learning approaches were used to screen the hub genes and immune cells. Finally, the diagnostic value of the hub genes was assessed by receiver operating characteristic (ROC) analysis. An experimental mouse model of dilated cardiomyopathy was used to validate the bioinformatics results. FRZB and EXT1 were identified as hub biomarkers, and the ROC curves suggested an excellent diagnostic ability of the above genes for DCM. In addition, naive B cells were upregulated in DCM tissues, while eosinophils, M2 macrophages, and memory CD4 T cells were downregulated in DCM tissues. The increase in two hub genes and naive B cells was validated in animal experiments. These results indicated that FRZB and EXT1 could be used as promising biomarkers, and eosinophils, M2 macrophages, resting memory CD4 T cells and naive B cells may also affect the occurrence of DCM. Show less
Neuritic plaques are one of the major pathological hallmarks of Alzheimer's disease. They are formed by the aggregation of extracellular amyloid-β protein (Aβ), which is derived from the sequential cl Show more
Neuritic plaques are one of the major pathological hallmarks of Alzheimer's disease. They are formed by the aggregation of extracellular amyloid-β protein (Aβ), which is derived from the sequential cleavage of amyloid-β precursor protein (APP) by β- and γ-secretase. BACE1 is the main β-secretase in the pathogenic process of Alzheimer's disease, which is believed to be a rate-limiting step of Aβ production. Presenilin 1 (PS1) is the active center of the γ-secretase that participates in the APP hydrolysis process. Mutations in the PS1 gene ( Show less
Ulcerative colitis (UC), a long-term inflammation of the colon, is a worldwide disease. Accumulating reports have suggested the contribution of environmental pollutants to UC development. As such, the Show more
Ulcerative colitis (UC), a long-term inflammation of the colon, is a worldwide disease. Accumulating reports have suggested the contribution of environmental pollutants to UC development. As such, the identification of biomarkers to evaluate pollutant-induced UC could provide a better assessment on the world's pollution problem. In the present study, we applied the plasma proteome to profile the plasma protein changes in three models: dextran sulfate sodium (DSS)-induced colitis, bisphenol A (BPA), and BPA-severe colitis. We aimed to investigate the functional roles of plasma proteins related to colitis development and further understand the synergistic effect of BPA on colitis. In addition, we aimed to identify novel biomarkers for UC non-invasive diagnosis and assessment of BPA-induced colitis. Our results showed a significant dysregulation of plasma proteins in these three models. Bioinformatics analysis, including gene ontology, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, and Ingenuity Pathway Analysis, highlighted the important effects of these dysregulated plasma proteins in immune and inflammatory responses through the regulation of CCR3 signaling in eosinophils, PI3K signaling in B lymphocytes, CD28 signaling in T helper cells, and leukocyte extravasation signaling in DSS-induced colitis model. Furthermore, our data suggested that BPA exposure altered the plasma proteins involved in lipid-related metabolic processes, leukocyte cell-cell adhesion and cytokine response. More importantly, we identified plasma proteins, ALB, APOA4, C3, CFB, DPEP1, HP, LTF, and Retnlg as biomarkers for assessing BPA-induced colitis. Show less
Agricultural use of neonicotinoid insecticides, neuroactive nitroguanidine compounds, has been detected everywhere in the global, posing significant hazard to nontarget organisms. This work studied th Show more
Agricultural use of neonicotinoid insecticides, neuroactive nitroguanidine compounds, has been detected everywhere in the global, posing significant hazard to nontarget organisms. This work studied the developmental neurotoxicity of zebrafish larvae exposed to imidacloprid (IMI) and thiamethoxam (THM), ranging from 0.05 µg L Show less
The liver is the center for uptake, synthesis, packaging, and secretion of lipids and lipoproteins. The research on lipid metabolism in pigs is limited. The objective of the present study is to identi Show more
The liver is the center for uptake, synthesis, packaging, and secretion of lipids and lipoproteins. The research on lipid metabolism in pigs is limited. The objective of the present study is to identify the genes related to lipid metabolism and oxidative stress in pigs by using transcriptomic analysis. Liver segments were collected from 60 Jinhua pigs for the determination of liver lipid content. The 7 pigs with the highest and lowest liver lipid content were set as group H and group L, respectively. Liver segments and serum samples were collected from each pig of the H and L groups for RNA sequencing and the determination of triglycerides (TG) content and high-density lipoprotein cholesterol (HDL) content, respectively. The HDL content in the serum of pigs in the H group was significantly higher than the L group ( Show less
Procymidone (PCM) is a low toxicity fungicide, and an endocrine-disrupting chemical (EDC) that particularly damages the reproductive system of male vertebrates. In present study, adolescent mice in co Show more
Procymidone (PCM) is a low toxicity fungicide, and an endocrine-disrupting chemical (EDC) that particularly damages the reproductive system of male vertebrates. In present study, adolescent mice in control, low-, medium-, and high-dose groups were orally administered 0 (equal volume of soybean oil), 50, 100, and 200 mg/kg/day PCM, respectively, for 21 days. Additionally, a three-dimensional culture of mouse testes was performed in vitro, and the control, low dose (0.33 × 10 Show less
Chicken internal organs are indispensable parts of the body, but their genetic architectures have not been commonly understood. Herein, we estimated the genetic parameters for heart weight (HW), liver Show more
Chicken internal organs are indispensable parts of the body, but their genetic architectures have not been commonly understood. Herein, we estimated the genetic parameters for heart weight (HW), liver weight (LW), spleen weight (SpW), testis weight (TW), glandular stomach weight (GSW), muscular stomach weight (MSW) and identified single nucleotide polymorphisms (SNPs) and potential candidate genes associated with internal organ weights in an F Show less
Glioblastoma (GBM) is the most common primary malignant brain tumor in adults. For patients with GBM, the median overall survival (OS) is 14.6 months and the 5-year survival rate is 7.2%. It is impera Show more
Glioblastoma (GBM) is the most common primary malignant brain tumor in adults. For patients with GBM, the median overall survival (OS) is 14.6 months and the 5-year survival rate is 7.2%. It is imperative to develop a reliable model to predict the survival probability in new GBM patients. To date, most prognostic models for predicting survival in GBM were constructed based on bulk RNA-seq dataset, which failed to accurately reflect the difference between tumor cores and peripheral regions, and thus show low predictive capability. An effective prognostic model is desperately needed in clinical practice. We studied single-cell RNA-seq dataset and The Cancer Genome Atlas-glioblastoma multiforme (TCGA-GBM) dataset to identify differentially expressed genes (DEGs) that impact the OS of GBM patients. We then applied the least absolute shrinkage and selection operator (LASSO) Cox penalized regression analysis to determine the optimal genes to be included in our risk score prognostic model. Then, we used another dataset to test the accuracy of our risk score prognostic model. We identified 2128 DEGs from the single-cell RNA-seq dataset and 6461 DEGs from the bulk RNA-seq dataset. In addition, 896 DEGs associated with the OS of GBM patients were obtained. Five of these genes (LITAF, MTHFD2, NRXN3, OSMR, and RUFY2) were selected to generate a risk score prognostic model. Using training and validation datasets, we found that patients in the low-risk group showed better OS than those in the high-risk group. We validated our risk score model with the training and validating datasets and demonstrated that it can effectively predict the OS of GBM patients. We constructed a novel prognostic model to predict survival in GBM patients by integrating a scRNA-seq dataset and a bulk RNA-seq dataset. Our findings may advance the development of new therapeutic targets and improve clinical outcomes for GBM patients. Show less
Mei Wang, Shaoqi Xu, Ya Li+8 more · 2022 · Comparative biochemistry and physiology. Part A, Molecular & integrative physiology · Elsevier · added 2026-04-24
Amylin is a 37-amino acid polypeptide that has been found to be involved in feeding regulation in some mammals, birds, and goldfish. We cloned amylin of Siberian sturgeon and detected its distribution Show more
Amylin is a 37-amino acid polypeptide that has been found to be involved in feeding regulation in some mammals, birds, and goldfish. We cloned amylin of Siberian sturgeon and detected its distribution pattern in 15 tissues. The expression levels in the periprandial period (pre-and post-feeding), the changes in the food intake, and the expression levels of related appetite factors after the intraperitoneal injection of amylin were detected. The expression of amylin was found to be the highest in the hypothalamus. Compared with 1 h pre-feeding, the expression levels of amylin in the hypothalamus and duodenum were increased significantly 1 h post-feeding. Compared with the control group (saline), intraperitoneal injection of 50 ng/g, 100 ng/g, and 200 ng/g of amylin significantly inhibited food intake at 1 h post injection, but not at 3 h and 6 h. The injection of 50 ng/g, 100 ng/g, and 200 ng/g amylin significantly inhibited the cumulative feed. After 1 h of 50 ng/g amylin injection, the levels of MC4R and somatostatin in the hypothalamus increased significantly, while the levels of amylin and NPY decreased significantly. The levels of CCK in the valvular intestine were increased significantly. Insulin in the duodenum was also increased significantly, but there was no significant change in ghrelin in the duodenum. These results show that amylin inhibits feeding in Siberian sturgeon by down-regulating the appetite-stimulating factor NPY and up-regulating the appetite-suppressing factors somatostatin, MC4R, CCK, and insulin. This study provides a theoretical basis for studying the feeding function and action mechanisms of amylin in Siberian sturgeon. Show less
Ovarian cancer (OC) has the lowest survival rate among gynecologic malignancies. Ectopic lymphocyte aggregates, namely tertiary lymphoid structures (TLSs), have been reported as positive biomarkers fo Show more
Ovarian cancer (OC) has the lowest survival rate among gynecologic malignancies. Ectopic lymphocyte aggregates, namely tertiary lymphoid structures (TLSs), have been reported as positive biomarkers for tumor prognosis. However, the related gene signature of tertiary lymphoid structure in ovarian cancer was less understood. Therefore, this study first exhibited the organizational patterns of tertiary lymphoid structure by H&E staining and immunohistochemistry (IHC), and confirmed the improved survival values of tertiary lymphoid structure and quantified tumor-infiltrating lymphocytes (CD20 Show less
Alzheimer disease (AD), a progressive neurodegenerative disorder, is mainly caused by the interaction of genetic and environmental factors. The impact of environmental factors on the genetic mutation Show more
Alzheimer disease (AD), a progressive neurodegenerative disorder, is mainly caused by the interaction of genetic and environmental factors. The impact of environmental factors on the genetic mutation in the amyloid precursor protein (APP) is not well characterized. We hypothesized that endoplasmic reticulum (ER) stress would promote disease for the patient carrying the APP D678H mutation. Therefore, we analyzed the impact of a familial AD mutation on amyloid precursor protein (APP D678H) under ER stress. Induced pluripotent stem cells (iPSCs) from APP D678H mutant carrier was differentiated into neurons, which were then analyzed for AD-like changes. Immunocytochemistry and whole-cell patch-clamp recording revealed that the derived neurons on day 28 after differentiation showed neuronal markers and electrophysiological properties similar to those of mature neurons. However, the APP D678H mutant neurons did not have significant alterations in the levels of amyloid-β (Aβ) and phosphorylated tau (pTau) compared to its isogenic wild-type neurons. Only under ER stress, the neurons with the APP D678H mutation had more Aβ and pTau via immune detection assays. The higher level of Aβ in the APP D678H mutant neurons was probably due to the increased level of β-site APP cleaving enzyme (BACE1) and decreased level of Aβ-degrading enzymes under ER stress. Increased Aβ and pTau under ER stress reduced the N-methyl-D-aspartate receptor (NMDAR) in Western blot analysis and altered electrophysiological properties in the mutant neurons. Our study provides evidence that the interaction between genetic mutation and ER stress would induce AD-like changes. Cover Image for this issue: https://doi.org/10.1111/jnc.15420. Show less
Adiponectin is a potent vascular protective molecule. Recent findings have suggested adiponectin resistance during early diabetes. However, the molecular mechanisms responsible remain unidentified. He Show more
Adiponectin is a potent vascular protective molecule. Recent findings have suggested adiponectin resistance during early diabetes. However, the molecular mechanisms responsible remain unidentified. Here, we took an unbiased approach to identify whether hyperlipidemic plasma molecules exist that bind and inhibit adiponectin function, contributing to adiponectin resistance and diabetic vascular injury. Adult rats were randomly assigned to receive either a normal or a high-fat diet for 8 weeks. Plasma was co-immunoprecipitated with anti-APN antibody and analyzed by mass spectrometry. The APN binding molecules and their effect upon APN biological activity were determined. As expected, the high-fat-diet increased plasma triglyceride, total cholesterol, and low-density lipoprotein. Importantly, the circulating APN level was significantly increased at this time point. Mass spectrometry identified 18 proteins with increased APN binding in hyperlipidemic plasma, among which four proteins critical in lipid metabolism, including apolipoprotein A1 (APOA1), APOA4, APOC1, and paraoxonase 1, were further investigated. Incubating recombinant APN with APOA1 markedly (P < 0.01), and incubating with APOC1 significantly (P < 0.05), inhibited APN activity as evidenced by the reduced AMPK activation in HUVECs. APOA4 and paraoxonase 1 incubation had no effect upon APN activity. Finally, plasma APOA1 was significantly increased (P < 0.05) in hyperlipidemic plasma compared with the control plasma. It was demonstrated for the first time that increased APOA1 and APOC1 in hyperlipidemic plasma binds and inhibits APN activity. This result not only identifies a novel molecular mechanism responsible for adiponectin resistance during early stage diabetes, but also provides additional new insight into the diverse/controversial (protective and harmful) functions of high-density lipoprotein. Show less
IKBKE, a non-canonical inflammatory kinase, is frequently amplified or activated, and plays predominantly oncogenic roles in human cancers, especially in breast cancer. However, the potential function Show more
IKBKE, a non-canonical inflammatory kinase, is frequently amplified or activated, and plays predominantly oncogenic roles in human cancers, especially in breast cancer. However, the potential function and underlying mechanism of IKBKE contributing to breast cancer metastasis remain largely elusive. Here, we report that depletion of Ikbke markedly decreases polyoma virus middle T antigen (PyVMT)-induced mouse mammary tumorigenesis and subsequent lung metastasis. Biologically, ectopic expression of IKBKE accelerates, whereas depletion of IKBKE attenuates breast cancer invasiveness and migration in vitro and tumor metastasis in vivo. Mechanistically, IKBKE tightly controls the stability of transcriptional factor Snail in different layers, in particular by directly phosphorylating Snail, which markedly blocks the E3 ligase β-TRCP1-mediated Snail degradation, resulting in breast cancer epithelial-mesenchymal transition (EMT) and metastasis. These findings together reveal a novel oncogenic function of IKBKE in promoting breast cancer metastasis by governing Snail abundance, and highlight the potential of targeting IKBKE for metastatic breast cancer therapies. Show less
Adult muscle stem cells, also known as satellite cells (SCs), play pivotal roles in muscle regeneration, and long non-coding RNA (lncRNA) functions in SCs remain largely unknown. Here, we identify a l Show more
Adult muscle stem cells, also known as satellite cells (SCs), play pivotal roles in muscle regeneration, and long non-coding RNA (lncRNA) functions in SCs remain largely unknown. Here, we identify a lncRNA, Lockd, which is induced in activated SCs upon acute muscle injury. We demonstrate that Lockd promotes SC proliferation; deletion of Lockd leads to cell-cycle arrest, and in vivo repression of Lockd in mouse muscles hinders regeneration process. Mechanistically, we show that Lockd directly interacts with RNA helicase DHX36 and the 5'end of Lockd possesses the strongest binding with DHX36. Furthermore, we demonstrate that Lockd stabilizes the interaction between DHX36 and EIF3B proteins; synergistically, this complex unwinds the RNA G-quadruplex (rG4) structure formed at Anp32e mRNA 5' UTR and promotes the translation of ANP32E protein, which is required for myoblast proliferation. Altogether, our findings identify a regulatory Lockd/DHX36/Anp32e axis that promotes myoblast proliferation and acute-injury-induced muscle regeneration. Show less
Hepatocellular carcinoma (HCC) stem cells are regarded as an important part of individualized HCC treatment and sorafenib resistance. However, there is lacking systematic assessment of stem-like indic Show more
Hepatocellular carcinoma (HCC) stem cells are regarded as an important part of individualized HCC treatment and sorafenib resistance. However, there is lacking systematic assessment of stem-like indices and associations with a response of sorafenib in HCC. Our study thus aimed to evaluate the status of tumor dedifferentiation for HCC and further identify the regulatory mechanisms under the condition of resistance to sorafenib. Datasets of HCC, including messenger RNAs (mRNAs) expression, somatic mutation, and clinical information were collected. The mRNA expression-based stemness index (mRNAsi), which can represent degrees of dedifferentiation of HCC samples, was calculated to predict drug response of sorafenib therapy and prognosis. Next, unsupervised cluster analysis was conducted to distinguish mRNAsi-based subgroups, and gene/geneset functional enrichment analysis was employed to identify key sorafenib resistance-related pathways. In addition, we analyzed and confirmed the regulation of key genes discovered in this study by combining other omics data. Finally, Luciferase reporter assays were performed to validate their regulation. Our study demonstrated that the stemness index obtained from transcriptomic is a promising biomarker to predict the response of sorafenib therapy and the prognosis in HCC. We revealed the peroxisome proliferator-activated receptor signaling pathway (the PPAR signaling pathway), related to fatty acid biosynthesis, that was a potential sorafenib resistance pathway that had not been reported before. By analyzing the core regulatory genes of the PPAR signaling pathway, we identified four candidate target genes, Show less
Clear cell renal cell carcinoma (ccRCC) accounts for 85% of all malignant renal tumors. Currently, the pathogenesis of ccRCC is not fully understood. Chromobox (CBX) family proteins are the major subu Show more
Clear cell renal cell carcinoma (ccRCC) accounts for 85% of all malignant renal tumors. Currently, the pathogenesis of ccRCC is not fully understood. Chromobox (CBX) family proteins are the major subunits of PcG complexes and are implicated in regulating mammalian development. The CBX family consists of eight members, namely, CBX1-8. Numerous studies have highlighted that each CBX protein exhibits distinct functions and prognostic roles in specific cancer types. In this study, in silico analysis indicated that CBX7 was downregulated in ccRCC and correlated with favorable prognosis in a ccRCC cohort. Subsequent studies showed that CBX7 inhibited cancer cell proliferation and invasion. Then, we showed that CBX7 downregulated ETS1 to inactivate the tumor necrosis factor (TNF) signaling pathway, which inhibited tumor proliferation and enhanced the sensitivity of ccRCC cells to tyrosine kinase inhibitors (TKIs). Moreover, we found that CBX7 was a bona fide substrate of RNF26. RNF26 promoted the degradation of CBX7 and enhanced ccRCC tumor growth. Therefore, our results revealed a novel RNF26/CBX7 axis that modulates the TNF signaling pathway in ccRCC. Show less
Lysyl-oxidase-like 3 (LOXL3) was reported to be essential in epithelial-mesenchymal transition (EMT) of cancers. However, the role of LOXL3 in hepatocellular carcinoma (HCC) remained unclear. In this Show more
Lysyl-oxidase-like 3 (LOXL3) was reported to be essential in epithelial-mesenchymal transition (EMT) of cancers. However, the role of LOXL3 in hepatocellular carcinoma (HCC) remained unclear. In this study, we explored clinical significance, biological functions, and regulatory mechanisms of LOXL3 in HCC. Our study found that LOXL3 expression was markedly associated with the tumor size and clinical stage of HCC, and it was highly expressed in tumor tissues of metastatic HCC patients. High expression of LOXL3 predicted a poor prognosis of HCC. TGF-β1 treatment elevated LOXL3 protein expression and cell invasion, and reduced cell apoptosis in HCC cell lines (SMMC-7721 and Huh-7), while downregulation of LOXL3 reversed the promotive effects of TGF-β1 treatment on LOXL3 protein expression and cell invasion, and the inhibitory effect on cell apoptosis. Mechanistically, LOXL3 interacted with snail family transcriptional repressor 1 (Snail1) through STRING database and RIP assay, and Snail1 bound to ubiquitin-specific peptidase 4 (USP4) promoter by JASPAR database, luciferase reporter gene and Co-IP assays. Overexpression of USP4 reversed the inhibitory effect of LOXL3 silence on EMT in HCC cells through deubiquitinating and stabilizing the expression of Snail1. Moreover, LOXL3-promoted HCC EMT through Wnt/β-catenin/Snail1 signaling pathway. In vivo study revealed that silence of LOXL3-inhibited HCC tumor growth. In conclusion, LOXL3 silence inhibited HCC invasion and EMT through Snail1/USP4-mediated circulation loop and Wnt/β-catenin signaling pathway. Show less
Heat stress is one of the most prevalent issues in poultry production that reduces performance, robustness, and economic gains. Previous studies have demonstrated that native chickens are more toleran Show more
Heat stress is one of the most prevalent issues in poultry production that reduces performance, robustness, and economic gains. Previous studies have demonstrated that native chickens are more tolerant of heat than commercial breeds. However, the underlying mechanisms of the heat tolerance observed in native chicken breeds remain unelucidated. Therefore, we performed a phenotypical, physiological, liver transcriptome comparative analysis and WGCNA in response to heat stress in one native (Beijing You, BY) and one commercial (Guang Ming, GM) chicken breed. The objective of this study was to evaluate the heat tolerance and identify the potential driver and hub genes related to heat stress in these two genetically distinct chicken breeds. In brief, 80 BY and 60 GM, 21 days old chickens were submitted to a heat stress experiment for 5 days (33 °C, 8 h/day). Each breed was divided into experimental groups of control (Ctl) and heat stress (HS). The results showed that BY chickens were less affected by heat stress and displayed reduced DEGs than GM chickens, 365 DEGs and 382 DEGs, respectively. The transcriptome analysis showed that BY chickens exhibited enriched pathways related to metabolism activity, meanwhile GM chickens' pathways were related to inflammatory reactions. Show less
Lung adenocarcinoma (LUAD) is a familiar lung cancer with a very poor prognosis. This study investigated the immune- and stemness-related genes to develop model related with cancer immunity and progno Show more
Lung adenocarcinoma (LUAD) is a familiar lung cancer with a very poor prognosis. This study investigated the immune- and stemness-related genes to develop model related with cancer immunity and prognosis in LUAD. The Cancer Genome Atlas (TCGA) was utilized for obtaining original transcriptome data and clinical information. Differential expression, prognostic value, and correlation with clinic parameter of mRNA stemness index (mRNAsi) were conducted in LUAD. Significant mRNAsi-related module and hub genes were screened using weighted gene coexpression network analysis (WGCNA). Meanwhile, immune-related differential genes (IRGs) were screened in LUAD. Stem cell index and immune-related differential genes (SC-IRGs) were screened and further developed to construct prognosis-related model and nomogram. Comprehensive analysis of hub genes and subgroups, involving enrichment in the subgroup [gene set enrichment analysis (GSEA)], gene mutation, genetic correlation, gene expression, immune, tumor mutation burden (TMB), and drug sensitivity, used bioinformatics and reverse transcription polymerase chain reaction (RT-PCR) for verification. Through difference analysis, mRNAsi of LUAD group was markedly higher than that of normal group. Clinical parameters (age, gender, and T staging) were ascertained to be highly relevant to mRNAsi. MEturquoise and MEblue were found to be the most significant modules (including positive and negative correlations) related to mRNAsi The SC-IRG model and the prognostic nomogram could accurately predict LUAD survival. Our study used mRNAsi combined with immunity that may lay a foundation for the future research studies in LUAD. Show less
DNA methylation plays a significant role in transducing external environmental signals to a cellular response in reptiles; however, whether the methylation patterns are conserved across species remain Show more
DNA methylation plays a significant role in transducing external environmental signals to a cellular response in reptiles; however, whether the methylation patterns are conserved across species remains unclear. Here, we examined the genome-wide DNA methylation differentiation between male and female hatchling gonads of the temperature-dependent sex determination (TSD) Mauremys mutica (M. mutica) using methylation-dependent restriction-site associated DNA sequencing (MethylRAD-seq) to test differentially methylated genes underlying sexual development. Several categories, including heat-shock genes (HSP90A, HSP30C), histone- (KDM8) and ubiquitin-related genes (TRIM39), kinases (WNK3), and gonad differentiation or gonadal-development-related genes (HSD17B8, HSD17B12), were identified as candidates for future study. Additionally, we identified several regulatory pathways potentially mediating TSD thermosensitivity such as the GnRH signaling pathway and calcium signaling pathway. These findings provide evidence that sexually dimorphic DNA methylation may be associated with sex determination or sex differentiation in TSD M. mutica. Show less
Fecundity in livestock is an economically important complex quantitative trait that is influenced by both genetics and the environment. However, the underlying genetic mechanism of reproductive perfor Show more
Fecundity in livestock is an economically important complex quantitative trait that is influenced by both genetics and the environment. However, the underlying genetic mechanism of reproductive performance in goats has not been well investigated. To investigate the genomic basis of fecundity in goats, genomic sequencing data of the Jining grey goat (a high prolificacy breed in China) were collected, as well as data for other commonly available goat breeds, and a mass of genomic variants were generated after variation calling. We screened the Jining grey goat (20 individuals) using a selective sweep with the Asian wild goat population (5 individuals), and potential candidate genes were proposed, such as STIM1, ESR1, LRRC14B and SLC9A3. Among, STIM1 is a most promising one associated with high reproductive capacity. When compared to Chinese domestic goats with low fecundity (17 individuals), the genes including MLLT10, SPIRE2, TCF25, ZNF276 and FANCA were screened, and the SPIRE2 gene was thought to be associated with fecundity traits. Meanwhile, the functional enrichment of these candidate genes revealed that they were involved in biological processes of mammary gland morphogenesis, uterus development, gastrulation, mesoderm morphogenesis and formation, and blood vessel development, which might undergo natural or artificial selection during reproductive trait formation in goats. Thus, our findings could enrich the genetic basis of reproductive trait selection during goat domestication, which may serve to improve goat breeding practices. Show less