title: An integrative transcriptomic analysis reveals bisphenol A exposure-induced dysregulation of microRNA expression in human endometrial cells.
abstract: Bisphenol A (BPA) are commonly used in the manufacture of polycarbonate plastics. Higher BPA exposure levels have been found in patients with endometrial hyperplasia that is one of risk factors of endometrial cancer (EC). Aberrant microRNAs (miRNAs) regulation has been observed in the development of cancer. Thus, this study investigated whether BPA exposure can disrupt miRNA regulation and its gene expression regarding to EC carcinogenic progress. Microarray experiments of miRNA and mRNA were performed in human endometrial cancer RL95-2 cells with treatment of low-to-moderate (10, 103and 105nM) BPA to explore the aberrant genes corresponding to human EC progression. According to the analysis of KEGG pathway and Cytoscape gene network, this study identified that BPA exposure reduced miR-149 expression to down-regulate DNA repair gene ARF6 (ADP-ribosylation factor 6) and tumor protein p53 (TP53), and up-regulate CCNE2 (cyclin E2) potentially to interrupt cell cycle. BPA also increased miR-107 to suppress hedgehog signaling factors, suppressor of fused homolog (SUFU) and GLI family zinc finger 3 (GLI3) to activate hedgehog signaling for cell proliferation underlying carcinogenesis. Furthermore, the BPA-induced cell proliferation was attenuated by transfection with miR-149 mimic and miR-107 inhibitor. These findings provided an insight into potential epigenetic mechanism of BPA exposure on the risk of endometrial carcinogenesis.
authors.affiliation: Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu, Taiwan; National Institute of Environmental Health Sciences, National Health Research Institute, Miaoli, Taiwan.
authors.forename: Wei-Chun
authors.initials: WC
authors.lastname: Chou
authors.affiliation: Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu, Taiwan.
authors.forename: Pei-Hsuan
authors.initials: PH
authors.lastname: Lee
authors.affiliation: Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu, Taiwan.
authors.forename: Yan-Yan
authors.initials: YY
authors.lastname: Tan
authors.affiliation: Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu, Taiwan.
authors.forename: Ho-Chen
authors.initials: HC
authors.lastname: Lin
authors.affiliation: Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu, Taiwan.
authors.forename: Chung-Wei
authors.initials: CW
authors.lastname: Yang
authors.affiliation: Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu, Taiwan.
authors.forename: Kuan-Hsueh
authors.initials: KH
authors.lastname: Chen
authors.affiliation: Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu, Taiwan. Electronic address: cychuang@mx.nthu.edu.tw.
authors.forename: Chun-Yu
authors.initials: CY
authors.lastname: Chuang
mesh_terms: D000089982:ADP-Ribosylation Factor 6; D001559:Benzhydryl Compounds / Q000633:toxicity*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D052244:Endocrine Disruptors / Q000633:toxicity*; D016889:Endometrial Neoplasms / Q000235:genetics*; D044127:Epigenesis, Genetic; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D010636:Phenols / Q000633:toxicity*; D012333:RNA, Messenger / Q000235:genetics; D000098826:Bisphenol A Compounds
chemical_list: D000089982:ADP-Ribosylation Factor 6; D001559:Benzhydryl Compounds; D052244:Endocrine Disruptors; D035683:MicroRNAs; D010636:Phenols; D012333:RNA, Messenger; C000715348:ARF6 protein, human; C006780:bisphenol A; D000098826:Bisphenol A Compounds
keywords: Bisphenol A; Carcinogenesis; Endometrial cancer; Gene network; Hedgehog signaling; MicroRNA