title: Hyper-methylated miR-203 dysregulates ABL1 and contributes to the nickel-induced tumorigenesis.
abstract: Nickel compounds have been found to be carcinogenic based upon epidemiological, animal and cell culture studies. Previous studies suggest that epigenetic mechanisms play a role in Nickel-induced carcinogenesis such as DNA methylation and histone modification. In this study, we investigated the role of microRNAs (miRNAs) in nickel-induced carcinogenesis. The expression of several miRNAs which may function as tumor suppressor genes revealed a strong downregulation of miR-203 in Ni3S2-transformed 16HBE cells (NSTCs). Meanwhile, we observed hypermethylation of CpGs in miR-203 promoter and first exon area, and proved that the hyper-methylated miR-203 was involved in the Nickel-induced tumorigenesis. Moreover, we identified that miR-203 may suppress the tumorigenesis at least in part through negatively regulating its target gene ABL1. Our findings indicate that DNA methylation-associated silencing of tumor suppressor miRNAs contributes to the development of Nickel-induced cancer.
authors: Translational Center for Stem Cell Research, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China; School of Life Science and Technology, Tongji University, Shanghai 200092, China. Electronic address: zhangjing@tongji.edu.cn.
authors: Jing
authors: J
authors: Zhang
authors: Yang
authors: Y
authors: Zhou
authors: You-Jun
authors: YJ
authors: Wu
authors: Meng-Jie
authors: MJ
authors: Li
authors: Rui-Jin
authors: RJ
authors: Wang
authors: Shun-Quan
authors: SQ
authors: Huang
authors: Rong-Rong
authors: RR
authors: Gao
authors: Lin
authors: L
authors: Ma
authors: Hong-Jun
authors: HJ
authors: Shi
authors: Jun
authors: J
authors: Zhang
mesh_terms: D000818:Animals; D001681:Biological Assay; D015153:Blotting, Western; D063646:Carcinogenesis / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism; D018899:CpG Islands; D019175:DNA Methylation / Q000187:drug effects*; D044127:Epigenesis, Genetic; D020868:Gene Silencing / Q000187:drug effects; D016147:Genes, Tumor Suppressor; D016313:Genes, abl; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D009532:Nickel / Q000633:toxicity*; D016374:Oncogene Proteins v-abl / Q000235:genetics / Q000378:metabolism; D012313:RNA / Q000737:chemistry / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction
chemical_list: C546703:MIRN203 microRNA, human; D035683:MicroRNAs; D016374:Oncogene Proteins v-abl; D012313:RNA; D009532:Nickel
keywords: ABL1; Hypermethylation; NSTCs; Ni(3)S(2)-transformed 16HBE cells; Nickel; Tumorigenesis; miR-203