title: OncomiR miR-96 and miR-182 promote cell proliferation and invasion through targeting ephrinA5 in hepatocellular carcinoma.
abstract: 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.
authors: Tissue Bank, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan.
authors: Tong-Hong
authors: TH
authors: Wang
authors: Liver Research Center, Department of Hepato-Gastroenterology, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan.
authors: Chau-Ting
authors: CT
authors: Yeh
authors: Department of Pathology and Graduate Institute of Pathology and Parasitology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors: Jar-Yi
authors: JY
authors: Ho
authors: Department of Anatomic Pathology, Chang Gung Memorial Hospital, Chang Gung University School of Medicine, Tao-Yuan, Taiwan.
authors: Kwai-Fong
authors: KF
authors: Ng
authors: Tissue Bank, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan.|Department of Anatomic Pathology, Chang Gung Memorial Hospital, Chang Gung University School of Medicine, Tao-Yuan, Taiwan.
authors: Tse-Ching
authors: TC
authors: Chen
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D036386:Ephrin-A5 / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics*; D009361:Neoplasm Invasiveness / Q000235:genetics* / Q000473:pathology
chemical_list: D036386:Ephrin-A5; C541492:MIRN96 microRNA, human; D035683:MicroRNAs; C538984:Mirn182 microRNA, human
keywords: ephrinA5; hepatocellular carcinoma; miR-182; miR-96