title: The alteration of miR-222 and its target genes in nickel-induced tumor.
abstract: Nickel is an important kind of metal and a necessary trace element in people's production and livelihood; it is also a well-confirmed human carcinogen. In the past few years, researchers did a large number of studies about the molecular mechanisms of nickel carcinogenesis, and they focused on activation of proto-oncogenes and inactivation of anti-oncogenes caused by gene point mutation, gene deletion, gene amplification, DNA methylation, chromosome condensation, and so on that were induced by nickel. However, the researches on tumorigenic molecular mechanisms regulated by microRNAs (miRNAs) are rare. In this study, we established nickel-induced tumor by injecting Ni3S2 compounds to Wistar Rattus. By establishing a cDNA library of miRNA from rat muscle tumor tissue induced by Ni3S2, we found that the expression of miR-222 was significantly upregulated in tumor tissue compared with the normal tissue. As we expected, the expression levels of target genes of miR-222, CDKN1B and CDKN1C, were downregulated in the nickel-induced tumor. The same alteration of miR-222 and its target genes was also found in malignant 16HBE cells induced with Ni3S2 compounds. We conclude that miR-222 may promote cell proliferation infinitely during nickel-induced tumorigenesis in part by regulating the expression of its target genes CDKN1B and CDKN1C. Our study elucidated a novel molecular mechanism of nickel-induced tumorigenesis.
authors: Tongji Hospital, Tongji University School of Medicine, 389 Xincun Road, Shanghai 200065, China. zhangjing@tongji.edu.cn
authors: Jing
authors: J
authors: Zhang
authors: Yang
authors: Y
authors: Zhou
authors: Lin
authors: L
authors: Ma
authors: Shunquan
authors: S
authors: Huang
authors: Ruijin
authors: R
authors: Wang
authors: Rongrong
authors: R
authors: Gao
authors: Youjun
authors: Y
authors: Wu
authors: Hongjun
authors: H
authors: Shi
authors: Jun
authors: J
authors: Zhang
mesh_terms: D000818:Animals; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D050760:Cyclin-Dependent Kinase Inhibitor p27; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D009369:Neoplasms / Q000139:chemically induced* / Q000378:metabolism*; D009532:Nickel / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction
chemical_list: C568897:MIRN222 microRNA, rat; D035683:MicroRNAs; D050760:Cyclin-Dependent Kinase Inhibitor p27; D009532:Nickel