title: miRNA-200c mediates mono-butyl phthalate-disrupted steroidogenesis by targeting vimentin in Leydig tumor cells and murine adrenocortical tumor cells.
abstract: The reproductive toxicity of plasticizer di-n-butyl phthalate (DBP) and its active metabolite monobutyl phthalate (MBP) has been demonstrated in rodents. The objective of this study was to explore roles of vimentin and miRNA-200c in steroidogenesis interfered by MBP. Mouse Leydig tumor cells (MLTC-1) and murine adrenocortical tumor cells (Y1) were employed and exposed to various levels of MBP (10(-7), 10(-6), 10(-5) and 10(-4)M). Steroid hormone production was increased significantly when MLTC-1 and Y1 cells were exposed to MBP at 10(-7)M. Additionally, vimentin and steroidogenic acute regulatory protein (StAR) expressions were upregulated at the same dose. It was found that MBP increased the steroidogenesis by facilitating the cholesterol transfer process by vimentin. In contrast, miRNA-200c expression was depressed at doses of MBP (10(-7)M) in both cells. Moreover, vimentin expression and progesterone production were increased in both MLTC-1 and Y1 cells after miRNA-200c expression was artificially inhibited. These results strongly suggested that MBP raised steroid hormone synthesis via upregulated vimentin by miRNA-200c.
authors.affiliation: The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China; The Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Hongchao
authors.initials: H
authors.lastname: Lu
authors.affiliation: The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China; The Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Chang
authors.initials: C
authors.lastname: Zhang
authors.affiliation: The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China; The Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 211166, China; Safety Assessment and Research Center for Drug, Pesticide and Veterinary Drug of Jiangsu Province, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Yanhui
authors.initials: Y
authors.lastname: Hu
authors.affiliation: The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China; The Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 211166, China; Safety Assessment and Research Center for Drug, Pesticide and Veterinary Drug of Jiangsu Province, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Heng
authors.initials: H
authors.lastname: Qin
authors.affiliation: The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China; The Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Aihua
authors.initials: A
authors.lastname: Gu
authors.affiliation: The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China; Department of Nutrition and Food Hygiene, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China; The Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 211166, China; Safety Assessment and Research Center for Drug, Pesticide and Veterinary Drug of Jiangsu Province, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Lulu
authors.initials: L
authors.lastname: Zhang
authors.affiliation: The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China; Department of Nutrition and Food Hygiene, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Li
authors.affiliation: The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China; The Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 211166, China; Safety Assessment and Research Center for Drug, Pesticide and Veterinary Drug of Jiangsu Province, Nanjing Medical University, Nanjing 211166, China. Electronic address: ncsa@njmu.edu.cn.
authors.forename: Yubang
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000306:Adrenal Cortex Neoplasms / Q000378:metabolism; D000818:Animals; D045744:Cell Line, Tumor; D003993:Dibutyl Phthalate / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D007984:Leydig Cell Tumor / Q000378:metabolism; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000187:drug effects / Q000378:metabolism*; D010750:Phosphoproteins / Q000187:drug effects; D011374:Progesterone / Q000096:biosynthesis; D013256:Steroids / Q000096:biosynthesis*; D014162:Transfection; D015854:Up-Regulation / Q000187:drug effects; D014746:Vimentin / Q000096:biosynthesis* / Q000187:drug effects*; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: D035683:MicroRNAs; C543719:Mirn200 microRNA, mouse; D010750:Phosphoproteins; D013256:Steroids; D014746:Vimentin; D000098682:Steroidogenic Acute Regulatory Protein; D003993:Dibutyl Phthalate; D011374:Progesterone
keywords: Monobutyl phthalate; Phthalate esters; Steroidogenesis; Vimentin; miRNA-200c