title: The Role of miR-182-5p in Hepatocarcinogenesis of Trichloroethylene in Mice.
abstract: Trichloroethylene (TCE), commonly used as an industrial solvent, is ubiquitous in our living environment. TCE exposure can induce hepatocellular carcinoma (HCC) in mice, but the underlying mechanisms remain elusive. To understand the role of miRNA in the hepatocarcinogenesis of TCE, we examined the miRNA expression profiles by microarray in the liver of B6C3F1 male mice exposed to TCE at 0 or 1000 mg/kg b.w. Nine differentially expressed miRNAs were identified, out of which miR-182-5p exhibited the highest increase in expression. Moreover, the TCE-induced upregulation of miR182-5p in mouse liver was dose dependent and correlated with promoter DNA hypomethylation. Treatment of mouse liver cell lines (BNL CL.2 and Hepa1-6) with TCE at non-toxic doses (0.1 and/or 0.3 mM) significantly increased the expression level of miR-182-5p accompanied with elevated cell proliferation. The TCE-induced cell proliferation was further found to be mediated by miR-182-5p overexpression. Additionally, tumor suppressor gene Cited2, which was downregulated in TCE exposed mouse liver cells, was proved to be a direct target of miR-182-5p. In conclusion, TCE might up-regulate miR-182-5p expression by DNA hypomethylation, which could suppress Cited2 and improve cell proliferation rate, resulting in liver tumor.
authors.affiliation: Department of Physiology, School of Biology and Basic Medical Sciences, Soochow University, Suzhou, China.|Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Soochow University, Suzhou, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Soochow University, Suzhou, China.|Department of Toxicology, School of Public Health, Soochow University, Suzhou, China.
authors.forename: Jiahong
authors.initials: J
authors.lastname: Chen
authors.affiliation: Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Soochow University, Suzhou, China.|Department of Toxicology, School of Public Health, Soochow University, Suzhou, China.
authors.forename: Cong
authors.initials: C
authors.lastname: Yue
authors.affiliation: Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Soochow University, Suzhou, China.|Department of Toxicology, School of Public Health, Soochow University, Suzhou, China.
authors.forename: Hang
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Soochow University, Suzhou, China.|Department of Toxicology, School of Public Health, Soochow University, Suzhou, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Tong
authors.affiliation: Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Soochow University, Suzhou, China.|Department of Toxicology, School of Public Health, Soochow University, Suzhou, China.
authors.forename: Jianxiang
authors.initials: J
authors.lastname: Li
authors.affiliation: Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Soochow University, Suzhou, China.|Department of Toxicology, School of Public Health, Soochow University, Suzhou, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Chen
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000187:drug effects*; D002273:Carcinogens / Q000633:toxicity*; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003433:Crosses, Genetic; D019175:DNA Methylation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D017930:Genes, Reporter / Q000187:drug effects; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000819:agonists* / Q000378:metabolism; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000187:drug effects; D012334:RNA, Neoplasm / Q000819:agonists / Q000378:metabolism; D011897:Random Allocation; D012097:Repressor Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D012997:Solvents / Q000633:toxicity; D015534:Trans-Activators / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D014241:Trichloroethylene / Q000633:toxicity*
chemical_list: D002273:Carcinogens; C110087:Cited2 protein, mouse; D035683:MicroRNAs; C540524:Mirn182 microRNA, mouse; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm; D012097:Repressor Proteins; D012997:Solvents; D015534:Trans-Activators; D014241:Trichloroethylene
keywords: trichloroethylene (TCE); miR-182-5p; DNA methylation; liver;
                      mouse.