📚 Article Archive

Polyunsaturated fatty acid biosynthesis pathway determines ferroptosis sensitivity in gastric cancer.

Ji-Yoon Lee, Miso Nam, Hye Young Son +21 more · 2020 · Proceedings of the National Academy of Sciences of the United States of America · National Academy of Sciences · added 2026-04-24

Ferroptosis is an iron-dependent regulated necrosis mediated by lipid peroxidation. Cancer cells survive under metabolic stress conditions by altering lipid metabolism, which may alter their sensitivi Show more

Ferroptosis is an iron-dependent regulated necrosis mediated by lipid peroxidation. Cancer cells survive under metabolic stress conditions by altering lipid metabolism, which may alter their sensitivity to ferroptosis. However, the association between lipid metabolism and ferroptosis is not completely understood. In this study, we found that the expression of elongation of very long-chain fatty acid protein 5 (ELOVL5) and fatty acid desaturase 1 (FADS1) is up-regulated in mesenchymal-type gastric cancer cells (GCs), leading to ferroptosis sensitization. In contrast, these enzymes are silenced by DNA methylation in intestinal-type GCs, rendering cells resistant to ferroptosis. Lipid profiling and isotope tracing analyses revealed that intestinal-type GCs are unable to generate arachidonic acid (AA) and adrenic acid (AdA) from linoleic acid. AA supplementation of intestinal-type GCs restores their sensitivity to ferroptosis. Based on these data, the polyunsaturated fatty acid (PUFA) biosynthesis pathway plays an essential role in ferroptosis; thus, this pathway potentially represents a marker for predicting the efficacy of ferroptosis-mediated cancer therapy. Show less

no PDF DOI: 10.1073/pnas.2006828117

FADS1

Roles of GPRC5 family proteins: focusing on GPRC5B and lipid-mediated signalling.

Yoshio Hirabayashi, Yeon-Jeong Kim · 2020 · Journal of biochemistry · Oxford University Press · added 2026-04-24

In the past decade, physiological roles and molecular functions of GPRC5 family receptors, originally identified as retinoic acid-induced gene products, have been uncovered, even though their intrinsi Show more

In the past decade, physiological roles and molecular functions of GPRC5 family receptors, originally identified as retinoic acid-induced gene products, have been uncovered, even though their intrinsic agonists are still a mystery. They are differentially distributed in certain tissues and cells in the body suggesting that cell-type-specific regulations and functions are significant. Molecular biological approaches and knockout mouse studies reveal that GPRC5 family proteins have pivotal roles in cancer progression and control of metabolic homeostasis pathways. Remarkably, GPRC5B-mediated tyrosine-phosphorylation signalling cascades play a critical role in development of obesity and insulin resistance through dynamic sphingolipid metabolism. Show less

no PDF DOI: 10.1093/jb/mvaa030

GPRC5B

Identification of Novel Genetic Variants Related to Trabecular Bone Score in Community-Dwelling Older Adults.

Sung Hye Kong, Ji Won Yoon, Jung Hee Kim +6 more · 2020 · Endocrinology and metabolism (Seoul, Korea) · added 2026-04-24

Sung Hye Kong, Ji Won Yoon, Jung Hee Kim, JooYong Park, Jiyeob Choi, Ji Hyun Lee, A Ram Hong, Nam H Cho, Chan Soo Shin Show less

As the genetic variants of trabecular bone microarchitecture are not well-understood, we performed a genome-wide association study to identify genetic determinants of bone microarchitecture analyzed b Show more

As the genetic variants of trabecular bone microarchitecture are not well-understood, we performed a genome-wide association study to identify genetic determinants of bone microarchitecture analyzed by trabecular bone score (TBS). TBS-associated genes were discovered in the Ansung cohort (discovery cohort), a community-based rural cohort in Korea, and then validated in the Gene-Environment Interaction and Phenotype (GENIE) cohort (validation cohort), consisting of subjects who underwent health check-up programs. In the discovery cohort, 2,451 participants were investigated for 1.42 million genotyped and imputed markers. In the validation cohort, identified as significant variants were evaluated in 2,733 participants. An intronic variant in iroquois homeobox 3 (IRX3), rs1815994, was significantly associated with TBS in men (P=3.74E-05 in the discovery cohort, P=0.027 in the validation cohort). Another intronic variant in mitogen-activated protein kinase kinase 5 (MAP2K5), rs11630730, was significantly associated with TBS in women (P=3.05E-09 in the discovery cohort, P=0.041 in the validation cohort). Men with the rs1815994 variant and women with the rs11630730 variant had lower TBS and lumbar spine bone mineral density. The detrimental effects of the rs1815994 variant in men and rs11630730 variant in women were also identified in association analysis (β=-0.0281, β=-0.0465, respectively). In this study, the rs1815994 near IRX3 in men and rs11630730 near MAP2K5 in women were associated with deterioration of the bone microarchitecture. It is the first study to determine the association of genetic variants with TBS. Further studies are needed to confirm our findings and identify additional variants contributing to the trabecular bone microarchitecture. Show less

📄 PDF DOI: 10.3803/EnM.2020.735

MAP2K5

The MEK5-ERK5 Kinase Axis Controls Lipid Metabolism in Small-Cell Lung Cancer.

Sandra Cristea, Garry L Coles, Daniel Hornburg +13 more · 2020 · Cancer research · added 2026-04-24

Sandra Cristea, Garry L Coles, Daniel Hornburg, Maya Gershkovitz, Julia Arand, Siqi Cao, Triparna Sen, Stuart C Williamson, Jun W Kim, Alexandros P Drainas, Andrew He, Laurent Le Cam, Lauren Averett Byers, Michael P Snyder, Kévin Contrepois, Julien Sage Show less

Small-cell lung cancer (SCLC) is an aggressive form of lung cancer with dismal survival rates. While kinases often play key roles driving tumorigenesis, there are strikingly few kinases known to promo Show more

Small-cell lung cancer (SCLC) is an aggressive form of lung cancer with dismal survival rates. While kinases often play key roles driving tumorigenesis, there are strikingly few kinases known to promote the development of SCLC. Here, we investigated the contribution of the MAPK module MEK5-ERK5 to SCLC growth. MEK5 and ERK5 were required for optimal survival and expansion of SCLC cell lines Show less

📄 PDF DOI: 10.1158/0008-5472.CAN-19-1027

MAP2K5

Glucosamine regulates hepatic lipid accumulation by sensing glucose levels or feeding states of normal and excess.

Jiwon Park, Yunkyoung Lee, Eun-Hye Jung +3 more · 2020 · Biochimica et biophysica acta. Molecular and cell biology of lipids · Elsevier · added 2026-04-24

Jiwon Park, Yunkyoung Lee, Eun-Hye Jung, Sang-Min Kim, Hyeongjin Cho, Inn-Oc Han Show less

Dose-dependent lipid accumulation was induced by glucose in HepG2 cells. GlcN also exerted a promotory effect on lipid accumulation in HepG2 cells under normal glucose conditions (NG, 5 mM) and liver Show more

Dose-dependent lipid accumulation was induced by glucose in HepG2 cells. GlcN also exerted a promotory effect on lipid accumulation in HepG2 cells under normal glucose conditions (NG, 5 mM) and liver of normal fed zebrafish larvae. High glucose (HG, 25 mM)-induced lipid accumulation was suppressed by l-glutamine-d-fructose 6-phosphate amidotransferase inhibitors. ER stress inhibitors did not suppress HG or GlcN-mediated lipid accumulation. HG and GlcN stimulated protein expression, DNA binding and O-GlcNAcylation of carbohydrate-responsive element-binding protein (ChREBP). Furthermore, both HG and GlcN increased nuclear sterol regulatory element-binding protein-1 (SREBP-1) levels in HepG2 cells. In contrast to its stimulatory effect under NG, GlcN suppressed lipid accumulation in HepG2 cells under HG conditions. Similarly, GlcN suppressed lipid accumulation in livers of overfed zebrafish. In addition, GlcN activity on DNA binding and O-GlcNAcylation of ChREBP was stimulatory under NG and inhibitory under HG conditions. Moreover, GlcN enhanced ChREBP, SREBP-1c, ACC, FAS, L-PK and SCD-1 mRNA expression under NG but inhibited HG-induced upregulation in HepG2 cells. The O-GlcNAc transferase inhibitor, alloxan, reduced lipid accumulation by HG or GlcN while the O-GlcNAcase inhibitor, PUGNAc, enhanced lipid accumulation in HepG2 cells and liver of zebrafish larvae. GlcN-induced lipid accumulation was inhibited by the AMPK activator, AICAR. Phosphorylation of AMPK (p-AMPK) was suppressed by GlcN under NG while increased by GlcN under HG. PUGNAc downregulated p-AMPK while alloxan restored GlcN- or HG-induced p-AMPK inhibition. Our results collectively suggest that GlcN regulates lipogenesis by sensing the glucose or energy states of normal and excess fuel through AMPK modulation. Show less

no PDF DOI: 10.1016/j.bbalip.2020.158764

MLXIPL

Carbohydrate responsive element binding protein (ChREBP) negatively regulates osteoblast differentiation via protein phosphatase 2A Cα dependent manner.

Kyeong-Min Kim, Eun-Jung Kim, Won-Gu Jang · 2020 · The international journal of biochemistry & cell biology · Elsevier · added 2026-04-24

Carbohydrate responsive element binding protein (ChREBP) is a major transcription factor of lipogenesis regulated by glucose status in the liver. However, the function of ChREBP in osteogenic differen Show more

Carbohydrate responsive element binding protein (ChREBP) is a major transcription factor of lipogenesis regulated by glucose status in the liver. However, the function of ChREBP in osteogenic differentiation is unclear. The present study examined the role of ChREBP in osteoblast differentiation in MC3T3-E1 preosteoblast cell line. The mRNA expression of ChREBP, protein phosphatase 2A catalytic subunit-α (PP2A Cα) and the osteogenic genes such as, DNA-binding protein inhibitor (Id1), runt-related transcription factor-2 (Runx2), and alkaline phosphatase (ALP) was measured by qPCR and RT-PCR. Runx2, ChREBP, and PP2A Cα, protein levels were evaluated by Western blotting. ALP staining experiment was carried out to evaluate ALP enzyme activity, and a luciferase reporter assay was performed to analyze Runx2 transcriptional activity. Expression of ChREBP and PP2A Cα did not change during bone morphogenetic protein-2 (BMP2)-induced osteoblast differentiation. Overexpression of ChREBP reduced the osteogenic genes (Runx2 and ALP) expression and ALP activity, while knockdown of ChREBP had the opposite effects. Overexpression of PP2A Cα increased ChREBP expression, while inhibition of PP2A Cα using okadaic acid not only inhibited the expression of ChREBP, but also restored the mRNA and protein expression of Runx2 and activity of ALP enzyme. These results demonstrate that ChREBP inhibits BMP2-induced osteoblast differentiation in a PP2A Cα- dependent manner. Show less

no PDF DOI: 10.1016/j.biocel.2020.105766

MLXIPL

Genotype-Related Clinical Characteristics and Myocardial Fibrosis and their Association with Prognosis in Hypertrophic Cardiomyopathy.

Hyung Yoon Kim, Jong Eun Park, Sang-Chol Lee +7 more · 2020 · Journal of clinical medicine · MDPI · added 2026-04-24

Hyung Yoon Kim, Jong Eun Park, Sang-Chol Lee, Eun-Seok Jeon, Young Keun On, Sung Mok Kim, Yeon Hyeon Choe, Chang-Seok Ki, Jong-Won Kim, Kye Hun Kim Show less

The spectrum of genetic variants and their clinical significance of Hypertrophic cardiomyopathy (HCM) have been poorly studied in Asian patients. The objectives of this study were to assess the spectr Show more

The spectrum of genetic variants and their clinical significance of Hypertrophic cardiomyopathy (HCM) have been poorly studied in Asian patients. The objectives of this study were to assess the spectrum of genetic variants and genotype-phenotype relationships within a Korean HCM population. Eighty-nine consecutive unrelated HCM patients were included. All patients underwent genotypic analysis for 23 HCM-associated genes. Clinical parameters including echocardiographic and cardiac magnetic resonance (CMR) parameters were evaluated. A composite of major adverse cardiac and cerebrovascular events was assessed. Genetic variants were detected in 55 of 89 subjects. Pathogenic variants or likely pathogenic variants were identified in 27 of HCM patients in Genetic variants in patients with HCM are relatively common and are associated with adverse clinical events and myocardial fibrosis on CMR. Genotypic analysis may add important information to clinical variables in the assessment of long-term risk for HCM patients. Show less

no PDF DOI: 10.3390/jcm9061671

MYBPC3

Differential contributions of sarcomere and mitochondria-related multigene variants to the endophenotype of hypertrophic cardiomyopathy.

Hyemoon Chung, Yoonjung Kim, Sun-Mi Cho +14 more · 2020 · Mitochondrion · Elsevier · added 2026-04-24

Hyemoon Chung, Yoonjung Kim, Sun-Mi Cho, Ho-Joon Lee, Chul-Hwan Park, Jong-Youn Kim, Sang-Hak Lee, Pil-Ki Min, Young Won Yoon, Byoung Kwon Lee, Woo-Shik Kim, Bum-Kee Hong, Tae Hoon Kim, Se-Joong Rim, Hyuck Moon Kwon, Eui-Young Choi, Kyung-A Lee Show less

Hypertrophic cardiomyopathy (HCM) is a multigenic disease that occurs due to various genetic modifiers. We investigated phenotype-based clinical and genetic characteristics of HCM patients using compr Show more

Hypertrophic cardiomyopathy (HCM) is a multigenic disease that occurs due to various genetic modifiers. We investigated phenotype-based clinical and genetic characteristics of HCM patients using comprehensive genetic tests and rare variant association analysis. A comprehensive HCM-specific panel, consisting of 82 nuclear DNAs (nDNAs: 33 sarcomere-associated genes, 5 phenocopy genes, and 44 nuclear genes linked to mitochondrial cardiomyopathy) and 37 mitochondrial DNAs (mtDNAs), was analyzed. Rare variant analysis was performed to determine the association of specific genes with different phenotypes. Among the 212 patients, pathogenic variants in sarcomere-associated genes were more prevalent in non-apical HCM (41.4%, 46/111; P = 0.001) than apical HCM (20.8%, 21/101). Apical HCM exhibits mild phenotypes than non-apical HCM, and it showed fewer numbers of sarcomere mutations than non-apical HCM. Interestingly, inverted mutation frequency of TNNI3 (35%) and MYH7 (9%) was observed in apical HCM. In a rare variant analysis, MT-RNR2 positively correlated with apical HCM (OR: 1.37, P = 0.025). And, MYBPC3 (sarcomere gene) negatively contributed to apical HCM (OR: 0.54, P = 0.027). On the other hand, both pathogenic mutation (P < 0.05) and rare variants in sarcomere-associated genes (OR: 2.78-3.47, P < 0.05) were related to diastolic dysfunction and left atrium remodeling, which correlated with poor prognosis in HCM patients. Our results provide a clue towards explaining the difference between the prevalence and phenotype of apical HCM in Asian populations, and a foundation for genetics-based approaches that may enable individualized risk stratification for HCM patients. Show less

no PDF DOI: 10.1016/j.mito.2020.04.010

MYBPC3

The Crucial Role of Xanthine Oxidase in CKD Progression Associated with Hypercholesterolemia.

You-Jin Kim, Se-Hyun Oh, Ji-Sun Ahn +5 more · 2020 · International journal of molecular sciences · MDPI · added 2026-04-24

You-Jin Kim, Se-Hyun Oh, Ji-Sun Ahn, Ju-Min Yook, Chan-Duck Kim, Sun-Hee Park, Jang-Hee Cho, Yong-Lim Kim Show less

In the present study, we investigated the effects of xanthine oxidase (XO) inhibition on cholesterol-induced renal dysfunction in chronic kidney disease (CKD) mice, and in low-density lipoprotein (LDL Show more

In the present study, we investigated the effects of xanthine oxidase (XO) inhibition on cholesterol-induced renal dysfunction in chronic kidney disease (CKD) mice, and in low-density lipoprotein (LDL)-treated human kidney proximal tubule epithelial (HK-2) cells. ApoE knockout (KO) mice underwent uninephrectomy to induce CKD, and were fed a normal diet or high-cholesterol (HC) diet along with the XO inhibitor topiroxostat (1 mg/kg/day). HK-2 cells were treated with LDL (200 µg/mL) and topiroxostat (5 µM) or small interfering RNA against xanthine dehydrogenase (siXDH; 20 nM). In uninephrectomized ApoE KO mice, the HC diet increased cholesterol accumulation, oxidative stress, XO activity, and kidney damage, while topiroxostat attenuated the hypercholesterolemia-associated renal dysfunction. The HC diet induced cholesterol accumulation by regulating the expressions of genes involved in cholesterol efflux ( Show less

no PDF DOI: 10.3390/ijms21207444

NR1H3

Cynandione A from Cynanchum wilfordii inhibits hepatic de novo lipogenesis by activating the LKB1/AMPK pathway in HepG2 cells.

Sunggun Kim, Yeo Yeong Yoon, Ye Won Park +3 more · 2020 · Journal of natural medicines · Springer · added 2026-04-24

Sunggun Kim, Yeo Yeong Yoon, Ye Won Park, Wan-Kyunn Whang, So-Young Park, Kwang Woo Hwang Show less

Cynandione A (CA), isolated from ethyl acetate extract of Cynanchum wilfordii (CW), is a bioactive phytochemical that has been found to be beneficial for the treatment of several diseases. Hepatic de Show more

Cynandione A (CA), isolated from ethyl acetate extract of Cynanchum wilfordii (CW), is a bioactive phytochemical that has been found to be beneficial for the treatment of several diseases. Hepatic de novo lipogenesis is one of the main causes of non-alcoholic fatty liver disease (NAFLD), which is thought to be a hepatic manifestation of certain metabolic syndromes. However, it has not yet been reported if CA has any therapeutic value in these diseases. Here, we investigated whether CA can inhibit hepatic lipogenesis induced by liver X receptor α (LXRα) using an in vitro model. We found that the extract and ethyl acetated layer of CW decreased the mRNA levels of sterol regulatory element-binding protein-1c (SREBP-1c), which plays a crucial role in hepatic lipogenesis. Additionally, we observed that CA could suppress the level of SREBP-1c, which was increased using two commercial LXRα agonists, GW3954 and T0901317. Moreover, the enzymes that act downstream of SREBP-1c were also inhibited by CA treatment. To understand the mechanism underlying this effect, the levels of phosphorylated AMP kinase (pAMPK) were measured after CA treatment. Therefore, CA might increase the pAMPK level by inducing phosphorylation of liver kinase B1 (LKB1), which can then convert AMPK to pAMPK. Taken together, we conclude that CA has an alleviative effect on hepatic lipogenesis through the stimulation of the LKB1/AMPK pathway. Show less

no PDF DOI: 10.1007/s11418-019-01356-x

NR1H3

Clinicopathologic Analysis of Cathepsin B as a Prognostic Marker of Thyroid Cancer.

Eun-Kyung Kim, Min-Jeong Song, Ho Hee Jang +1 more · 2020 · International journal of molecular sciences · MDPI · added 2026-04-24

Eun-Kyung Kim, Min-Jeong Song, Ho Hee Jang, Yoo Seung Chung Show less

Thyroid cancer incidence has increased worldwide; however, investigations of thyroid cancer-related factors as potential prognosis markers remain insufficient. Secreted proteins from the cancer secret Show more

Thyroid cancer incidence has increased worldwide; however, investigations of thyroid cancer-related factors as potential prognosis markers remain insufficient. Secreted proteins from the cancer secretome are regulators of several molecular mechanisms and are, thereby, ideal candidates for potential markers. We aimed to identify a specific factor for thyroid cancer by analyzing the secretome from normal thyroid cells, papillary thyroid cancer (PTC) cells, and anaplastic thyroid cancer cells using mass spectrometry (MS). Cathepsin B (CTSB) showed highest expression in PTC cells compared to other cell lines, and CTSB levels in tumor samples were higher than that seen in normal tissue. Further, among thyroid cancer patients, increased CTSB expression was related to higher risk of lymph node metastasis (LNM) and advanced N stage. Overexpression of CTSB in thyroid cancer cell lines activated cell migration by increasing the expression of vimentin and Snail, while its siRNA-mediated silencing inhibited cell migration by decreasing vimentin and Snail expression. Mechanistically, CTSB-associated enhanced cell migration and upregulation of vimentin and Snail occurred via increased phosphorylation of p38. As our results suggest that elevated CTSB in thyroid cancer induces the expression of metastatic proteins and thereby leads to LNM, CTSB may be a good and clinically relevant prognostic marker. Show less

no PDF DOI: 10.3390/ijms21249537

SNAI1

Metastatic behavior analyses of tetraspanin TM4SF5-expressing spheres in three-dimensional (3D) cell culture environment.

Dae-Geun Song, Eunmi Kim, Jung Weon Lee · 2020 · Archives of pharmacal research · Springer · added 2026-04-24

Cancer metastasis involves diverse cellular functions via bidirectional communications between intracellular and extracellular spaces. To achieve development of the anti-metastatic drugs, one needs to Show more

Cancer metastasis involves diverse cellular functions via bidirectional communications between intracellular and extracellular spaces. To achieve development of the anti-metastatic drugs, one needs to consider the efficacy and mode of action (MOA) of the drug candidates to block the metastatic potentials of cancerous cells. Rather than under two-dimensional environment, investigation of the metastatic potentials under three-dimensional environment would be much pharmaceutically beneficent, since it can mimic the in vivo tumor lesions in cancer patients, leading to allowance of drug candidates analyzed in the 3D culture systems to lower failure rates during the anti-metastatic drug development. Here we have reviewed on the analyses of metastatic potentials of certain cancer models in 3D culture systems surrounded with extracellular matrix proteins, which could be supported by TM4SF5- and/or EMT-mediated actions. We particularly focused the initial events of the cancer metastasis, such as invasive outgrowth and dissemination from the cancer cell masses, spheroids, embedded in the 3D gel culture systems. This review summarizes the significance of tetraspanin TM4SF5 and Snail1 that are related to EMT in the metastatic potentials explored in the 3D gel systems. Show less

no PDF DOI: 10.1007/s12272-020-01291-6

SNAI1

Breast Cancer Subtypes Underlying EMT-Mediated Catabolic Metabolism.

Eunae Sandra Cho, Nam Hee Kim, Jun Seop Yun +3 more · 2020 · Cells · MDPI · added 2026-04-24

Eunae Sandra Cho, Nam Hee Kim, Jun Seop Yun, Sue Bean Cho, Hyun Sil Kim, Jong In Yook Show less

Efficient catabolic metabolism of adenosine triphosphate (ATP) and reduced nicotinamide adenine dinucleotide phosphate (NADPH) is essentially required for cancer cell survival, especially in metastati Show more

Efficient catabolic metabolism of adenosine triphosphate (ATP) and reduced nicotinamide adenine dinucleotide phosphate (NADPH) is essentially required for cancer cell survival, especially in metastatic cancer progression. Epithelial-mesenchymal transition (EMT) plays an important role in metabolic rewiring of cancer cells as well as in phenotypic conversion and therapeutic resistance. Snail (SNAI1), a well-known inducer of cancer EMT, is critical in providing ATP and NADPH via suppression of several gatekeeper genes involving catabolic metabolism, such as phosphofructokinase 1 (PFK1), fructose-1,6-bisphosphatase 1 (FBP1), and acetyl-CoA carboxylase 2 (ACC2). Paradoxically, PFK1 and FBP1 are counter-opposing and rate-limiting reaction enzymes of glycolysis and gluconeogenesis, respectively. In this study, we report a distinct metabolic circuit of catabolic metabolism in breast cancer subtypes. Interestingly, PFKP and FBP1 are inversely correlated in clinical samples, indicating different metabolic subsets of breast cancer. The luminal types of breast cancer consist of the pentose phosphate pathway (PPP) subset by suppression of PFKP while the basal-like subtype (also known as triple negative breast cancer, TNBC) mainly utilizes glycolysis and mitochondrial fatty acid oxidation (FAO) by loss of FBP1 and ACC2. Notably, PPP remains active via upregulation of TIGAR in the FBP1-loss basal-like subset, indicating the importance of PPP in catabolic cancer metabolism. These results indicate different catabolic metabolic circuits and thus therapeutic strategies in breast cancer subsets. Show less

no PDF DOI: 10.3390/cells9092064

SNAI1

Slug is a novel molecular target for head and neck squamous cell carcinoma stem-like cells.

Jung Hwa Moon, Sang Hyuk Lee, Bon Seok Koo +6 more · 2020 · Oral oncology · Elsevier · added 2026-04-24

Jung Hwa Moon, Sang Hyuk Lee, Bon Seok Koo, Jin Man Kim, Songmei Huang, Jae Hoon Cho, Young Gyu Eun, Hyang Ae Shin, Young Chang Lim Show less

The acquisition of stem-like phenotype is partly attributed to the induction of epithelial-mesenchymal transition (EMT). Thus, the activation of factors involved in EMT can be linked to cancer stem ce Show more

The acquisition of stem-like phenotype is partly attributed to the induction of epithelial-mesenchymal transition (EMT). Thus, the activation of factors involved in EMT can be linked to cancer stem cell genesis. However, the underlying mechanisms in head and neck squamous cell carcinoma (HNSCC) remain largely unknown. Herein, we investigate whether slug, one of the major effectors of EMT, affects the stemness of HNSCC cells. We performed in vitro experiments to determine whether slug gene manipulation can influence the stemness phenotypes, including the capacity for self-renewal, expression of putative stemness markers, chemoresistance, and invasion in HNSCC cells. Further, we identified whether Slug knockout attenuates tumorigenicity of HNSCC cells in vivo. Finally, we examined whether prognosis of HNSCC patients after curative treatment may be affected by the level of slug expression. Overexpression of slug promoted self-renewal of HNSCC cells via activation of sphere formation, the expression of stem cell markers, and induction of chemoresistance to cisplatin. Also, slug overexpression increased the migration and invasion of HNSCC cells in vitro and was mainly observed during the invasion in HNSCC xenograft mouse model. By contrast, slug expression knockdown abrogated their self-renewal capacity, stemness-associated gene expression, and cisplatin chemoresistance. Furthermore, high levels of slug expression correlated with poor prognosis of patients with HNSCC. Inhibition of slug expression may represent a novel therapeutic strategy targeting HNSCC stem-like cells. Show less

no PDF DOI: 10.1016/j.oraloncology.2020.104948

SNAI1

Diospyros kaki leaves inhibit HGF/Met signaling-mediated EMT and stemness features in hepatocellular carcinoma.

Hyeonseok Ko, Gyuwon Huh, Sang Hoon Jung +4 more · 2020 · Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association · Elsevier · added 2026-04-24

Hyeonseok Ko, Gyuwon Huh, Sang Hoon Jung, Hyukjoon Kwon, Youngsic Jeon, Young Nyun Park, Young-Joo Kim Show less

Persimmon (Diospyros kaki L.f.) trees are widely cultivated for their edible fruits in Asia. D. kaki leaves are abundant in phytochemicals that have numerous medicinal properties. Hepatocyte growth fa Show more

Persimmon (Diospyros kaki L.f.) trees are widely cultivated for their edible fruits in Asia. D. kaki leaves are abundant in phytochemicals that have numerous medicinal properties. Hepatocyte growth factor (HGF) and its receptor Met lead to poor prognosis via the promotion of metastasis and chemoresistance in hepatocellular carcinoma (HCC). Therefore, inhibitors targeting the HGF/Met pathway are regarded as promising drugs against HCC. Here, we investigated the effects of D. kaki leaves on HGF-induced epithelial-to-mesenchymal transition (EMT) and stemness traits in HCC. The ethanol extract of D. kaki leaves (EEDK) markedly suppressed HGF-mediated cell migration and invasion through upregulation of CDH1 and downregulation of SNAI1, VIM, MMP1, MMP2, and MMP9. Moreover, EEDK increased the cytotoxicity of sorafenib, which was reduced by HGF, and decreased the expression of the stemness markers KRT19 and CD44. Additionally, we found a clear correlation between stemness and EMT markers in HCC patients. Importantly, EEDK reduced Met activity and attenuated HGF-mediated activation of JNK/c-Jun. Our findings provide new evidence that EEDK can ameliorate HCC with poor prognosis and aggressive phenotype by blocking HGF/Met signaling. Show less

no PDF DOI: 10.1016/j.fct.2020.111475

SNAI1

Snail augments fatty acid oxidation by suppression of mitochondrial ACC2 during cancer progression.

Ji Hye Yang, Nam Hee Kim, Jun Seop Yun +11 more · 2020 · Life science alliance · added 2026-04-24

Ji Hye Yang, Nam Hee Kim, Jun Seop Yun, Eunae Sandra Cho, Yong Hoon Cha, Sue Bean Cho, Seon-Hyeong Lee, So Young Cha, Soo-Youl Kim, Jiwon Choi, Tin-Tin Manh Nguyen, Sunghyouk Park, Hyun Sil Kim, Jong In Yook Show less

Despite the importance of mitochondrial fatty acid oxidation (FAO) in cancer metabolism, the biological mechanisms responsible for the FAO in cancer and therapeutic intervention based on catabolic met Show more

Despite the importance of mitochondrial fatty acid oxidation (FAO) in cancer metabolism, the biological mechanisms responsible for the FAO in cancer and therapeutic intervention based on catabolic metabolism are not well defined. In this study, we observe that Snail (SNAI1), a key transcriptional repressor of epithelial-mesenchymal transition, enhances catabolic FAO, allowing pro-survival of breast cancer cells in a starved environment. Mechanistically, Snail suppresses mitochondrial ACC2 (ACACB) by binding to a series of E-boxes located in its proximal promoter, resulting in decreased malonyl-CoA level. Malonyl-CoA being a well-known endogenous inhibitor of fatty acid transporter carnitine palmitoyltransferase 1 (CPT1), the suppression of ACC2 by Snail activates CPT1-dependent FAO, generating ATP and decreasing NADPH consumption. Importantly, combinatorial pharmacologic inhibition of pentose phosphate pathway and FAO with clinically available drugs efficiently reverts Snail-mediated metabolic reprogramming and suppresses in vivo metastatic progression of breast cancer cells. Our observations provide not only a mechanistic link between epithelial-mesenchymal transition and catabolic rewiring but also a novel catabolism-based therapeutic approach for inhibition of cancer progression. Show less

no PDF DOI: 10.26508/lsa.202000683

SNAI1

AKT drives sustained motility following MEK inhibition via promoting SNAIL and AXL in MDA-MB-231 LM2.

Junyeob Kwon, David M Helfman, Mi-Young Kim · 2020 · Biochemical and biophysical research communications · Elsevier · added 2026-04-24

The adaptive activation of alternative signaling pathways contributes to acquired resistance against targeted cancer therapies. Our previous research has shown that blocking Ras/ERK signaling promotes Show more

The adaptive activation of alternative signaling pathways contributes to acquired resistance against targeted cancer therapies. Our previous research has shown that blocking Ras/ERK signaling promotes PI3K/AKT signaling in the lung metastatic derivative of MDA-MB-231 (LM2). Because AKT activation was required to drive sustained cell motility following MEK suppression, we extend our research to elucidate how activation of the PI3K/AKT signaling drives sustained motility following MEK inhibition. Reverse phase protein array (RPPA) revealed that SNAIL (SNAI1) was upregulated in U0126 (MEK inhibitor)-treated LM2 cells. Importantly, LM2 cells simultaneously treated with U0126 and PI3K inhibitor LY294002 exhibited reduced expression of SNAIL. Furthermore, depletion of SNAIL led to reduced cell motility in U0126-treated LM2 cells. In addition, we identified AXL as another downstream effector of AKT. These results suggest that SNAIL and AXL are key factors mediating sustained motility of LM2 cells following MEK suppression. Because AKT mediates motile behavior under MEK suppression, our results suggest that AKT and AXL may be targeted to overcome resistance against drugs targeting the Ras/ERK pathway. Show less

no PDF DOI: 10.1016/j.bbrc.2020.05.043

SNAI1

A rapid quantification of invasive phenotype in head and neck squamous cell carcinoma: A novel 3D pillar array system.

Sung Yong Choi, Dong Woo Lee, Bokhyun Song +5 more · 2020 · Oral oncology · Elsevier · added 2026-04-24

Sung Yong Choi, Dong Woo Lee, Bokhyun Song, Soo Yoon Kim, Hye Jin Kim, Da-Yong Shin, Bosung Ku, Man Ki Chung Show less

The widely used in vitro invasion assays for head and neck squamous cell carcinoma (HNSCC) are wound healing, transwell, and organotypic assays. However, these are still lab-intensive and time-consumi Show more

The widely used in vitro invasion assays for head and neck squamous cell carcinoma (HNSCC) are wound healing, transwell, and organotypic assays. However, these are still lab-intensive and time-consuming tasks. For the rapid detection and high throughput screening of invasiveness in 3D condition, we propose a novel spheroid invasion assay using commercially available pillar platform system. Using the pillar-based spheroid invasion assay, migration and invasion was evaluated in three patient-derived cells (PDCs) of HNSCC. Immunofluorescence of live cells was used for the quantitative measurement of migratory and invaded cells attached to the pillar. Expression of epithelial-mesenchymal transition (EMT)-related gene (snai1/2) was measured by qRT-PCR. We also tested the impact of drug treatments (cisplatin, docetaxel) on the changes in the invasive phenotype. All PDCs successfully formed spheroid at 4 days and can be measured invasiveness within 7 days. Intriguingly, one PDC (#1) obtained from the advanced stage showed robust migration, invasion and higher transcription of snai1/2, compared with the other two PDCs. Furthermore, the invasion ratio of the control spheroids was about 70% while the invasion ratios of drug-treated spheroids were lower than 50%, and the difference showed statistical significance (p < 0.01). The presented spheroid invasion assay using pillar array could be useful for the evaluation of cancer cell behavior and physiology in response to diverse therapeutic drugs. Show less

no PDF DOI: 10.1016/j.oraloncology.2020.104807

SNAI1

Amentoflavone, active compound of Selaginella tamariscina, inhibits in vitro and in vivo TGF-β-induced metastasis of human cancer cells.

Gye Lim Kim, Eun Hyang Jang, Da-Eun Lee +8 more · 2020 · Archives of biochemistry and biophysics · Elsevier · added 2026-04-24

Gye Lim Kim, Eun Hyang Jang, Da-Eun Lee, Chaeeun Bang, Haewon Kang, SooHyeon Kim, So Young Yoon, Do Hyun Lee, Jin Hee Na, Sangmin Lee, Jong-Ho Kim Show less

Epithelial mesenchymal transition (EMT) is a well-known and important step in metastasis and thus can be a key target in cancer treatment. Here, we tested the EMT inhibitory actions of Selaginella tam Show more

Epithelial mesenchymal transition (EMT) is a well-known and important step in metastasis and thus can be a key target in cancer treatment. Here, we tested the EMT inhibitory actions of Selaginella tamariscina and its active component, amentoflavone (AF). EMT was examined in vitro using wound-healing and invasion assays and by monitoring changes in the expression of the EMT-related proteins, E-cadherin, Snail, and Twist. Metastasis was examined in vivo using SCID mice injected with luciferase-labeled A549 cells. We confirmed that aqueous extracts of S. tamariscina (STE) and AF inhibited EMT in human cancer cell lines. We found that STE and AF at nontoxic concentrations exerted remarkable inhibitory effects on migration (wound healing assay) and invasion (Transwell assay) in tumor necrosis factor (TGF)-β-treated cancer cells. Western blotting and immunofluorescence imaging show that AF treatment also restored E-cadherin expression in these cells compared to cells treated with TGF-β only. Suppression of metastasis by AF was investigated by monitoring migration of tail-vein-injected, circulating A549-luc cells to the lungs in mice. After 3 wk, fewer nodules were observed in mice co-treated with AF compared with those treated with TGF-β only. Our findings indicate that STE and AF are promising EMT inhibitors and, ultimately, potentially potent antitumor agents. Show less

no PDF DOI: 10.1016/j.abb.2020.108384

SNAI1

Mesenchymal and MAPK Expression Signatures Associate with Telomerase Promoter Mutations in Multiple Cancers.

Josh Lewis Stern, Grace Hibshman, Kevin Hu +6 more · 2020 · Molecular cancer research : MCR · added 2026-04-24

Josh Lewis Stern, Grace Hibshman, Kevin Hu, Sarah E Ferrara, James C Costello, William Kim, Pablo Tamayo, Thomas R Cech, Franklin W Huang Show less

In a substantial fraction of cancers

no PDF DOI: 10.1158/1541-7786.MCR-19-1244

SNAI1

Host Genetic and Gut Microbial Signatures in Familial Inflammatory Bowel Disease.

Yoo Min Park, Eunji Ha, Ki-Nam Gu +4 more · 2020 · Clinical and translational gastroenterology · added 2026-04-24

Yoo Min Park, Eunji Ha, Ki-Nam Gu, Ga Young Shin, Chang Kyun Lee, Kwangwoo Kim, Hyo Jong Kim Show less

The family history of inflammatory bowel disease (IBD) has been strongly associated with risk of developing IBD. This study aimed to identify the host genetic and gut microbial signatures in familial Show more

The family history of inflammatory bowel disease (IBD) has been strongly associated with risk of developing IBD. This study aimed to identify the host genetic and gut microbial signatures in familial IBD. Genetic analyses using genome-wide single nucleotide polymorphism genotyping and whole exome sequencing were performed to calculate weighted genetic risk scores from known IBD-associated common variants and to identify rare deleterious protein-altering variants specific to patients with familial IBD in 8 Korean families that each included more than 2 affected first-degree relatives (FDRs) and their unaffected FDR(s). In parallel, gut microbial community was analyzed by 16S rRNA sequencing of stools from the sample individuals. The risk of familial IBD was not well explained by the genetic burden from common IBD-risk variants, suggesting the presence of family-shared genetic and environmental disease-risk factors. We identified 17 genes (AC113554.1, ACE, AKAP17A, AKAP9, ANK2, ASB16, ASIC3, DNPH1, DUS3L, FAM200A, FZD10, LAMA5, NUTM2F, PKN1, PRR26, WDR66, and ZC3H4) that each contained rare, potentially deleterious variants transmitted to the affected FDRs in multiple families. In addition, metagenomic analyses revealed significantly different diversity of gut microbiota and identified a number of differentially abundant taxa in affected FDRs, highlighting 22 novel familial disease-associated taxa with large abundance changes and the previously reported gut dysbiosis including low alpha diversity in IBD and 16 known IBD-specific taxa. This study identified familial IBD-associated rare deleterious variants and gut microbial dysbiosis in familial IBD. Show less

no PDF DOI: 10.14309/ctg.0000000000000213

ZC3H4

MC4R and HNF4α promoter methylation at birth contribute to triglyceride levels in childhood: A prospective cohort study.

Eun Jin Kwon, Hye Ah Lee, Young-Ah You +5 more · 2019 · Medicine · added 2026-04-24

Eun Jin Kwon, Hye Ah Lee, Young-Ah You, Jae Young Yoo, Hyesook Park, Eun Ae Park, Eun Hee Ha, Young Ju Kim Show less

Although the changes in DNA methylation are assumed to be due to the association between adverse intrauterine conditions and adult metabolic health, evidence from human studies is rare. Little is know Show more

Although the changes in DNA methylation are assumed to be due to the association between adverse intrauterine conditions and adult metabolic health, evidence from human studies is rare. Little is known about the changes in DNA methylation present at birth that affect metabolic profiles in childhood. Previous studies have shown that the melanocortin 4 receptor (MC4R) and hepatocyte nuclear factor 4 alpha (HNF4α) genes are associated with obesity and metabolic disorders. Thus, we investigated the associations of the DNA methylation statuses of MC4R and HNF4α in cord blood with metabolic profiles in childhood.We collected data from 90 children 7 to 9 years of age included in the Ewha Birth & Growth Cohort Study in Korea. DNA methylation was analyzed by pyrosequencing. The children were split into 2 groups according to the cutoff triglyceride (TG) levels (<110 and ≥110 mg/dL).The methylation statuses of MC4R and HNF4α at birth were significantly associated with the TG level in childhood (P < .05). It was interesting to note that the methylation statuses of MC4R and HNF4α in cord blood were significantly decreased, whereas childhood body mass index was significantly increased, in children with high TG levels compared with children with low TG levels (P < .05).Our findings show that the methylation statuses of MC4R and HNF4α at birth are associated with metabolic profiles in childhood. These epigenetic modifications occurring in early life may contribute to subsequent metabolic-related disorders. Thus, we suggest that DNA methylation status in cord blood may be predictive of the risk of developing metabolic syndrome. Show less

📄 PDF DOI: 10.1097/MD.0000000000016424

MC4R

The neuroplastic effect of olfactory training to the recovery of olfactory system in mouse model.

Boo-Young Kim, Ju Yeon Park, Eui Jin Kim +3 more · 2019 · International forum of allergy & rhinology · Wiley · added 2026-04-24

Boo-Young Kim, Ju Yeon Park, Eui Jin Kim, Byung Guk Kim, Sung Won Kim, Soo Whan Kim Show less

Several studies have reported the benefits of olfactory training (OT) in the olfactory nervous system of mouse models. Therefore, in this study we performed next-generation sequencing to evaluate the Show more

Several studies have reported the benefits of olfactory training (OT) in the olfactory nervous system of mouse models. Therefore, in this study we performed next-generation sequencing to evaluate the effects of OT on mRNA sequencing in the olfactory area. Mice in each group were administered 300 mg of 3-methylindole per kilogram of mouse weight. The olfactory function was evaluated by a food-finding test once a week. The olfactory neuroepithelium was harvested for histologic examination and protein analysis. Subsequently, data analysis, gene ontology and pathway analysis, quantitative real-time polymerase chain reaction of mRNA, and Western blot analysis were conducted. Mice were divided into 4 groups according to treatment. Control, anosmia, training, and steroid group mice resumed food finding. Olfactory Maker Protein, olfr1507, ADCY3, and GNAL mRNA expression was higher in the olfactory neuroepithelium of OT than anosmia group mice. In total, 26,364 mRNAs were analyzed. Comparison of the results of OT vs anosmia revealed that ADCY8,10, GFAP, NGF, NGFR, GFAP, and BDNF mRNAs were upregulated in the gene ontology. OT improved olfactory function, as indicated by the food-finding test. OT improved the olfactory recovery time to stimulate olfactory nerve regeneration. OT may initially stimulate the olfactory receptor, followed by neurogenesis. Steroid therapy and OT operated under completely different mechanisms in the upregulated gene study. These results indicate that OT may be one of the future modalities for treating olfactory impairment. Show less

📄 PDF DOI: 10.1002/alr.22320

ADCY3

Antiinflammatory activity of ANGPTL4 facilitates macrophage polarization to induce cardiac repair.

Dong Im Cho, Hye-Jin Kang, Ju Hee Jeon +9 more · 2019 · JCI insight · added 2026-04-24

Dong Im Cho, Hye-Jin Kang, Ju Hee Jeon, Gwang Hyeon Eom, Hyang Hee Cho, Mi Ra Kim, Meeyoung Cho, Hye-Yun Jeong, Hyen Chung Cho, Moon Hwa Hong, Yong Sook Kim, Youngkeun Ahn Show less

Mesenchymal stem cells (MSCs) can suppress pathological inflammation. However, the mechanisms underlying the association between MSCs and inflammation remain unclear. Under coculture conditions with m Show more

Mesenchymal stem cells (MSCs) can suppress pathological inflammation. However, the mechanisms underlying the association between MSCs and inflammation remain unclear. Under coculture conditions with macrophages, MSCs highly expressed angiopoietin-like 4 (ANGPTL4) to blunt the polarization of macrophages toward the proinflammatory phenotype. ANGPTL4-deficient MSCs failed to inhibit the inflammatory macrophage phenotype. In inflammation-related animal models, the injection of coculture medium or ANGPTL4 protein increased the antiinflammatory macrophages in both peritonitis and myocardial infarction. In particular, cardiac function and pathology were markedly improved by ANGPTL4 treatment. We found that retinoic acid-related orphan receptor α (RORα) was increased by inflammatory mediators, such as IL-1β, and bound to ANGPTL4 promoter in MSCs. Collectively, RORα-mediated ANGPTL4 induction was shown to contribute to the antiinflammatory activity of MSCs against macrophages under pathological conditions. This study suggests that the capability of ANGPTL4 to induce tissue repair is a promising opportunity for safe stem cell-free regeneration therapy from a translational perspective. Show less

no PDF DOI: 10.1172/jci.insight.125437

ANGPTL4

Transcriptome analysis after PPARγ activation in human meibomian gland epithelial cells (hMGEC).

Sun Woong Kim, Donald J Brown, James V Jester · 2019 · The ocular surface · Elsevier · added 2026-04-24

PPARγ plays a critical role in the maturation of immortalized human meibomian gland epithelial cells (hMGEC). To further understand the molecular changes associated with meibocyte differentiation, we Show more

PPARγ plays a critical role in the maturation of immortalized human meibomian gland epithelial cells (hMGEC). To further understand the molecular changes associated with meibocyte differentiation, we analyzed transcriptome profiles from hMGEC after PPARγ activation. Three sets of cultivated hMGEC with or without exposure to PPARγ agonist, rosiglitazone were used for RNA-seq analysis. RNA was isolated and processed to generate 6 libraries. The libraries were then sequenced and mapped to the human reference genome, and the expression results were gathered as reads per length of transcript in kilobases per million mapped reads (RPKM) values. Differential gene expression analyses were performed using DESeq2 and NOISeq. Gene ontology enrichment analysis (GOEA) was performed on gene sets that were upregulated or downregulated after rosiglitazone treatment. Five genes were selected for validation and differential expression was confirmed using quantitative PCR. The Differential expression of CK5 was evaluated using Western blotting. Expression data indicated that about 58,000 genes are expressed in hMGEC. DESeq2 and NOISeq indicated that 296 and 3436 genes were upregulated and 258 and 3592 genes were down regulated after rosiglitazone treatment, respectively. Of genes showing significant differences > 2 fold, GOEA indicated that cellular and metabolic processes were highly represented. Expression of ANGPTL4, PLIN2, SQSTM1, and DDIT3 were significantly upregulated and HHIP was downregulated by rosiglitazone. CK5 was downregulated by rosiglitazone. The RNA-seq data suggested that PPARγ activation induced alterations in cell differentiation and metabolic process and affected multiple signaling pathways such as PPAR, autophagy, WNT, and Hedgehog. Show less

📄 PDF DOI: 10.1016/j.jtos.2019.02.003

ANGPTL4

Persistent changes in liver methylation and microbiome composition following reversal of diet-induced non-alcoholic-fatty liver disease.

Hyejin Kim, Oliver Worsley, Edwin Yang +11 more · 2019 · Cellular and molecular life sciences : CMLS · Springer · added 2026-04-24

Hyejin Kim, Oliver Worsley, Edwin Yang, Rikky Wenang Purbojati, Ai Leng Liang, Wilson Tan, Daniela I Drautz Moses, Septian Hartono, Vanessa Fan, Tony Kiat Hon Lim, Stephan C Schuster, Roger Sy Foo, Pierce Kah Hoe Chow, Sven Pettersson Show less

Non-alcoholic fatty liver disease (NAFLD) is a metabolic liver disease that is thought to be reversible by changing the diet. To examine the impact of dietary changes on progression and cure of NAFLD, Show more

Non-alcoholic fatty liver disease (NAFLD) is a metabolic liver disease that is thought to be reversible by changing the diet. To examine the impact of dietary changes on progression and cure of NAFLD, we fed mice a high-fat diet (HFD) or high-fructose diet (HFrD) for 9 weeks, followed by an additional 9 weeks, where mice were given normal chow diet. As predicted, the diet-induced NAFLD elicited changes in glucose tolerance, serum cholesterol, and triglyceride levels in both diet groups. Moreover, the diet-induced NAFLD phenotype was reversed, as measured by the recovery of glucose intolerance and high cholesterol levels when mice were given normal chow diet. However, surprisingly, the elevated serum triglyceride levels persisted. Metagenomic analysis revealed dietary-induced changes of microbiome composition, some of which remained altered even after reversing the diet to normal chow, as illustrated by species of the Odoribacter genus. Genome-wide DNA methylation analysis revealed a "priming effect" through changes in DNA methylation in key liver genes. For example, the lipid-regulating gene Apoa4 remained hypomethylated in both groups even after introduction to normal chow diet. Our results support that dietary change, in part, reverses the NAFLD phenotype. However, some diet-induced effects remain, such as changes in microbiome composition, elevated serum triglyceride levels, and hypomethylation of key liver genes. While the results are correlative in nature, it is tempting to speculate that the dietary-induced changes in microbiome composition may in part contribute to the persistent epigenetic modifications in the liver. Show less

no PDF DOI: 10.1007/s00018-019-03114-4

APOA4

Association of BUD13-ZNF259-APOA5-APOA1-SIK3 cluster polymorphism in 11q23.3 and structure of APOA5 with increased plasma triglyceride levels in a Korean population.

Han-Kyul Kim, Muhammad Ayaz Anwar, Sangdun Choi · 2019 · Scientific reports · Nature · added 2026-04-24

In this association study on chromosome 11, the data from 12,537 Korean individuals within the Health Examinee (HEXA) and the Korea Association Resource (KARE) projects were analysed to identify genet Show more

In this association study on chromosome 11, the data from 12,537 Korean individuals within the Health Examinee (HEXA) and the Korea Association Resource (KARE) projects were analysed to identify genetic loci correlating with increased and decreased plasma triglyceride (TG) levels. We identified a locus in chromosomal region 11q23.3 that harbours genes BUD13, ZNF259, APOA5, APOA1, and SIK3, which may be associated with plasma TG levels. In this locus, 13 relevant single-nucleotide polymorphisms (SNPs) were found: rs184616707, rs118175510, rs60954647, rs79408961, and rs180373 (near BUD13); rs11604424 (in ZNF259); rs2075291, rs651821, and rs7123666 (in or near APOA5); rs525028 (near APOA1), and rs645258, rs10160754, and rs142395187 (in or near SIK3). All 13 SNPs satisfied the genome-wide significance level (P < 5.0 × 10 Show less

📄 PDF DOI: 10.1038/s41598-019-44699-x

APOA5

Longitudinal interaction between APOA5 -1131T>C and overweight in the acceleration of age-related increase in arterial stiffness through the regulation of circulating triglycerides.

Minjoo Kim, Hye Jin Yoo, Hwa Jin Lee +1 more · 2019 · Hypertension research : official journal of the Japanese Society of Hypertension · Nature · added 2026-04-24

Minjoo Kim, Hye Jin Yoo, Hwa Jin Lee, Jong Ho Lee Show less

We aimed to evaluate whether the longitudinal interaction between APOA5-1131C variants and overweight could accelerate age-related increases in arterial stiffness and circulating triglycerides in heal Show more

We aimed to evaluate whether the longitudinal interaction between APOA5-1131C variants and overweight could accelerate age-related increases in arterial stiffness and circulating triglycerides in healthy subjects. This 3-year prospective cohort study included 503 healthy subjects. Brachial-ankle pulse wave velocity (baPWV), triglycerides, APOA5 -1131T > C, apolipoprotein (apo) A-V level, and low-density lipoprotein (LDL) particle size were measured at baseline and within a mean follow-up period of 3 years. At the 3-year follow-up, in the overweight group, subjects with the C allele showed increases in triglycerides and baPWV relative to baseline. Additionally, in the overweight group, there was a genotype effect on changes in triglycerides: subjects with the C allele had greater increases in triglyceride concentrations than subjects with the TT genotype. Furthermore, overweight subjects with the C allele had greater increases in triglyceride concentrations than normal-weight subjects with the C allele (P-interaction = 0.013). Overweight subjects with the C allele had greater increases in baPWV than normal-weight subjects with the C allele (P-interaction = 0.047). Changes in baPWV were affected by age, baseline baPWV, and changes in systolic blood pressure (BP) and triglycerides. Changes in triglycerides were affected by APOA5 -1131T > C genotype, age, baseline triglyceride level, and changes in BMI and apo A-V. In the overweight group, changes in baPWV were affected by changes in systolic BP, LDL particle size, and triglycerides. This prospective study shows that the interactive effect between APOA5 -1131C variants and overweight can accelerate age-related increase in arterial stiffness via the regulation of circulating triglycerides in healthy subjects. Show less

no PDF DOI: 10.1038/s41440-018-0137-y

APOA5

Effects of Obesity and Family History of Diabetes on the Association of

Jae Woong Sull, Soriul Kim, Sun Ha Jee · 2019 · Journal of lipid and atherosclerosis · added 2026-04-24

The aim of this study was to examine the associations of cholesterol ester transfer protein ( We analyzed the association of We found that the These findings indicate that

📄 PDF DOI: 10.12997/jla.2019.8.2.252

CETP

Cuban Sugar Cane Wax Acid and Policosanol Showed Similar Atheroprotective Effects with Inhibition of LDL Oxidation and Cholesteryl Ester Transfer via Enhancement of High-Density Lipoproteins Functionality.

Kyung-Hyun Cho, Myung-Ae Bae, Jae-Ryong Kim · 2019 · Cardiovascular therapeutics · added 2026-04-24

Cuban sugarcane wax acids (SCWA) and policosanol (PCO) are mixtures of higher aliphatic acids and alcohols, respectively, purified from sugarcane wax with different chief components. Although it has b Show more

Cuban sugarcane wax acids (SCWA) and policosanol (PCO) are mixtures of higher aliphatic acids and alcohols, respectively, purified from sugarcane wax with different chief components. Although it has been known that they have antioxidant and anti-inflammatory activities, physiological properties on molecular mechanism of SCWA have been less studied than PCO. In this study, we compared antiatherogenic activities of SCWA and PCO via encapsulation with reconstituted high-density lipoproteins (rHDL). After reconstitution, SCWA-rHDL showed smaller particle size than PCO-rHDL with increase of content. PCO-rHDL or SCWA-rHDL showed distinct inhibition of glycation with similar extent in the presence of fructose. PCO-rHDL or SCWA-rHDL showed strong antioxidant activity against cupric ion-mediated oxidation of low-density lipoproteins (LDL), and inhibition of oxLDL uptake into macrophages. Although PCO-rHDL showed 1.2-fold stronger inhibition against cholesteryl ester transfer protein (CETP) activity than SCWA-rHDL, SCWA-rHDL enhanced 15% more brain cell (BV-2) growth and 23% more regeneration of tail fin in zebrafish. PCO and SCWA both enhance the beneficial functions of HDL to maximize its antioxidant, antiglycation, and antiatherosclerotic activities and the inhibition of CETP. These enhancements of HDL functionality by PCO and SCWA could exert antiaging and rejuvenation activity. Show less

📄 PDF DOI: 10.1155/2019/8496409

CETP

👤 Hong Sug Kim