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

Oncotarget. 2015 Sep 22;6(28):25962-74. doi: 10.18632/oncotarget.4504.

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.

Keywords: HBx; hepatocellular carcinoma cell; maspin; metastasis; microRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics
  • Anoikis / drug effects
  • Anoikis / genetics
  • Antineoplastic Agents / pharmacology
  • Blotting, Western
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / virology
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cell Survival / genetics
  • Disease Progression
  • Female
  • Gene Expression Profiling / methods
  • Gene Expression Regulation, Neoplastic
  • HEK293 Cells
  • Hep G2 Cells
  • Hepatitis B virus / genetics
  • Hepatitis B virus / metabolism
  • Hepatitis B virus / physiology
  • Host-Pathogen Interactions / genetics
  • Humans
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / virology
  • Male
  • MicroRNAs / genetics*
  • Multivariate Analysis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Serpins / genetics*
  • Serpins / metabolism
  • Trans-Activators / genetics*
  • Trans-Activators / metabolism
  • Viral Regulatory and Accessory Proteins

Substances

  • 3' Untranslated Regions
  • Antineoplastic Agents
  • MIRN107 microRNA, human
  • MIRN21 microRNA, human
  • MIRN7 microRNA, human
  • MicroRNAs
  • SERPIN-B5
  • Serpins
  • Trans-Activators
  • Viral Regulatory and Accessory Proteins
  • hepatitis B virus X protein

Associated data

  • GEO/GSE56424