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OncomiR miR-96 and miR-182 promote cell proliferation and invasion through targeting ephrinA5 in hepatocellular carcinoma

Wang, Tong-Hong, Yeh, Chau-Ting, Ho, Jar-Yi, Ng, Kwai-Fong, Chen, Tse-Ching·2016·Molecular Carcinogenesis
DOI 10.1002/mc.22286
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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.

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Metadata

Authors
Wang, T.-H., Yeh, C.-T., Ho, J.-Y., Ng, K.-F., & Chen, T.-C.
Affiliations
  • Tissue Bank; Chang Gung Memorial Hospital; Tao-Yuan Taiwan
  • Liver Research Center; Department of Hepato-Gastroenterology; Chang Gung Memorial Hospital; Tao-Yuan Taiwan
  • Department of Pathology and Graduate Institute of Pathology and Parasitology; Tri-Service General Hospital; National Defense Medical Center; Taipei Taiwan
  • Department of Anatomic Pathology; Chang Gung Memorial Hospital; Chang Gung University School of Medicine; Tao-Yuan Taiwan
Venue
Molecular Carcinogenesis
Publisher
Wiley
Published
2015-02-08
Volume
55
Issue
4
Pages
366-375
ISSN
0899-1987
DOI
10.1002/mc.22286
Cited by
58
References
2
Language
en
Licence
Funders
  • National Science Council, Taiwan (103-2320-B-182A-003)
  • Chang Gung Medical Research Program, Taiwan (CMRPG3D1321, CMRPG3A1183, CMRPG391494)

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