title: Alterations in microRNA expression linked to microcystin-LR-induced tumorigenicity in human WRL-68 Cells.
abstract: Microcystin-LR (MC-LR) is a cyclic heptapeptide that acts as a potent hepatotoxin and carcinogen. However, the mechanism of its carcinogenic action remains undetermined. In this study, MC-LR was used to induce the malignant transformation of the WRL-68 cell line. Alterations in microRNA (miRNA) expression in the transformed cell were analyzed to determine the role of miRNAs in MC-LR-induced carcinogenesis. Cultured WRL-68 cells (labeled 25MC10) were continuously exposed to a low concentration (10 μg/L) of MC-LR for 25 passages. Compared with the mock-treated parental cells, the induced 25MC10 cells exhibited a higher growth rate, resistance to serum-induced terminal differentiation, and tumorigenicity in a nude mouse xenograft test. A pilot miRNA expression array analysis was conducted on the 25MC10 cells, followed by validation of select miRNAs by RT-PCR. We found that the onco-miRNAs miR-21 and miR-221 displayed upregulated expression while the liver-specific miR-122 was downregulated. These results suggest that chronic MC-LR exposure alters the miRNA expression profile of WRL-68 cells and causes phenotypic transformation. We propose that characteristic miRNA alterations could be used as molecular targets for the development of environmental water monitoring methods.
authors.affiliation: Jiangsu Key Laboratory of Molecular Medicine, Nanjing University School of Medicine, Nanjing 210093, China.
authors.forename: Lizhi
authors.initials: L
authors.lastname: Xu
authors.forename: Wendi
authors.initials: W
authors.lastname: Qin
authors.forename: Huan
authors.initials: H
authors.lastname: Zhang
authors.forename: Yucai
authors.initials: Y
authors.lastname: Wang
authors.forename: Huan
authors.initials: H
authors.lastname: Dou
authors.forename: Decai
authors.initials: D
authors.lastname: Yu
authors.forename: Yitao
authors.initials: Y
authors.lastname: Ding
authors.forename: Liuyan
authors.initials: L
authors.lastname: Yang
authors.forename: Yaping
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced; D006801:Humans; D008099:Liver / Q000187:drug effects; D008387:Marine Toxins; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000378:metabolism*; D052998:Microcystins / Q000633:toxicity*; D014873:Water Pollutants / Q000633:toxicity*
chemical_list: D002273:Carcinogens; D008387:Marine Toxins; D035683:MicroRNAs; D052998:Microcystins; D014873:Water Pollutants; C525709:MIR221, human; C546122:MIRN221 microRNA, mouse; C057862:cyanoginosin LR