Long non-coding RNA TUSC7 acts a molecular sponge for miR-10a and suppresses EMT in hepatocellular carcinoma

Tumour Biol. 2016 Aug;37(8):11429-41. doi: 10.1007/s13277-016-4892-6. Epub 2016 Mar 22.

Abstract

Despite advances in the roles of long non-coding RNA (lncRNA) tumor suppressor candidate 7 (TUSC7) in cancer biology, which has been identified as a tumor suppressor by regulating cell proliferation, apoptosis, migration, invasion, cell cycle, and tumor growth, the function of TUSC7 in hepatocellular carcinoma (HCC) remains unknown. In this study, we observed that the expression of TUSC7 was immensely decreased in HCC. Clinically, the lower expression of TUSC7 predicted poorer survival and may be an independent risk factor for HCC patients. Moreover, TUSC7 inhibited cell metastasis, invasion, and epithelial-to-mesenchymal transformation (EMT) through competitively binding miR-10a. Furthermore, we found that TUSC7 could decrease the expression of Eph tyrosine kinase receptor A4 (EphA4), a downstream target of miR-10a as well as an EMT suppressor, through TUSC7-miR-10a-EphA4 axis. Taken together, we demonstrate that TUSC7 suppresses EMT through the TUSC7-miR-10a-EphA4 axis, which may be a potential target for therapeutic intervention in HCC.

Keywords: EMT; EphA4; HCC; TUSC7; miR-10a.

MeSH terms

  • Adult
  • Aged
  • Blotting, Western
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / mortality
  • Carcinoma, Hepatocellular / pathology*
  • Disease-Free Survival
  • Epithelial-Mesenchymal Transition / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic / genetics*
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Liver Neoplasms / genetics
  • Liver Neoplasms / mortality
  • Liver Neoplasms / pathology*
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Prognosis
  • Proportional Hazards Models
  • RNA, Long Noncoding / genetics*
  • Real-Time Polymerase Chain Reaction
  • Receptor, EphA4 / biosynthesis
  • Receptor, EphA4 / genetics
  • Transfection

Substances

  • MIRN10 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • Receptor, EphA4