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OncomiR miR‐96 and miR‐182 promote cell proliferation and invasion through targeting ephrinA5 in hepatocellular carcinoma
Author(s) -
Wang TongHong,
Yeh ChauTing,
Ho JarYi,
Ng KwaiFong,
Chen TseChing
Publication year - 2016
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.22286
Subject(s) - biology , microrna , oncomir , hepatocellular carcinoma , cancer research , downregulation and upregulation , cell growth , translation (biology) , suppressor , blot , cell , messenger rna , cancer , gene , genetics
EphrinA5, a member of the ephrinA subclass, is downregulated in hepatocellular carcinoma (HCC) and acts as a tumor suppressor. However, the upstream regulation mechanism of ephrinA5 remains unclear. In this study, we tried to identify and characterize the roles of miR‐96 and miR‐182 in the regulation of ephrinA5 expression in HCC. The expression levels of miR‐96 and miR‐182 were examined in 47 paired HCC and para‐tumoral liver tissues using quantitative real‐time RT‐PCR. The luciferase reporter assay and western blotting were employed to dissect the association between miR‐96/182 and ephrinA5 expression. Moreover, cells were treated with synthetic miR‐96/182 precursors and inhibitors to assess their effects on HCC cell growth and migration. It was found that both miR‐96 and miR‐182 were upregulated in HCC compared to para‐tumoral normal tissues. The expression of miR‐96 and miR‐182 was inversely associated with ephrinA5 protein levels. Furthermore, both miR‐96 and miR‐182 directly targeted the 3'UTR of the ephrinA5 mRNA and suppressed protein translation. The suppression of miR‐96 and miR‐182 led to reduced HCC cell proliferation and migration by negatively regulating ephrinA5 expression. In conclusion, miR‐96 and miR‐182 may act as oncomiRs in HCC by suppressing the expression of ephrinA5 and may play important roles in hepatocarcinogenesis. © 2015 Wiley Periodicals, Inc.