miRNA-7/21/107 contribute to HBx-induced hepatocellular carcinoma progression through suppression of maspin

Wen Shu Chen, Chia Jui Yen, Yun Ju Chen, Jhen Yu Chen, Li Yun Wang, Shu Jun Chiu, Wen Ling Shih, Chien Yi Ho, Tzu Tang Wei, Hsiao Lin Pan, Pei Hsuan Chien, Mien Chie Hung, Ching Chow Chen, Wei Chien Huang

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25 Citations (Scopus)

Abstract

Maspin suppresses tumor progression by promoting cell adhesion and apoptosis and by inhibiting cell motility. However, its role in tumorigenesis of hepatocellular carcinoma (HCC) remains unclear. The gene regulation of maspin and its relationship with HCC patient prognosis were investigated in this study. Maspin expression was specifically reduced in HBV-associated patients and correlated with their poor prognosis. Maspin downregulation in HCC cells was induced by HBx to promote their motility and resistance to anoikis and chemotherapy. HBx-dependent induction of microRNA-7, -107, and -21 was further demonstrated to directly target maspin mRNA, leading to its protein downregulation. Higher expressions of these microRNAs also correlated with maspin downregulation in HBV-associated patients, and were associated with their poor overall survival. These data not only provided new insights into the molecular mechanisms of maspin deficiency by HBx, but also indicated that downregulation of maspin by microRNAs confers HBx-mediated aggressiveness and chemoresistance in HCC.

Original languageEnglish
Pages (from-to)25962-25974
Number of pages13
JournalOncotarget
Volume6
Issue number28
DOIs
Publication statusPublished - 2015

All Science Journal Classification (ASJC) codes

  • Oncology

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    Chen, W. S., Yen, C. J., Chen, Y. J., Chen, J. Y., Wang, L. Y., Chiu, S. J., Shih, W. L., Ho, C. Y., Wei, T. T., Pan, H. L., Chien, P. H., Hung, M. C., Chen, C. C., & Huang, W. C. (2015). miRNA-7/21/107 contribute to HBx-induced hepatocellular carcinoma progression through suppression of maspin. Oncotarget, 6(28), 25962-25974. https://doi.org/10.18632/oncotarget.4504