Long non-coding RNA HNF1A-AS1 functioned as an oncogene and autophagy promoter in hepatocellular carcinoma through sponging hsa-miR-30b-5p

Biochem Biophys Res Commun. 2016 May 13;473(4):1268-1275. doi: 10.1016/j.bbrc.2016.04.054. Epub 2016 Apr 13.

Abstract

Long non-coding RNAs (lncRNAs) had been proved to be pivotal regulators in carcinogenesis. On the basis of competitive endogenous RNAs (ceRNAs) system, lncRNAs significantly expanded their regulating networks. In our research, we aimed to figure out the exact role of lncRNA HNF1A-AS1 in the pathogenesis of hepatocellular carcinoma (HCC), in a ceRNA-dependent way. First, we revealed: HNF1A-AS1 was frequently overexpressed in HCC tissues and cell lines and its relative high expression was closely related to larger tumor size, multiple tumor lesions, poor differentiation and advanced TNM stage. Then we found: HNF1A-AS1 functioned as an oncogene in tumor growth and apoptosis through sponging tumor-suppressive hsa-miR-30b-5p (miR-30b) and de-repressing Bcl-2. Further experiments identified: HNF1A-AS1-miR-30b axis significantly promoted autophagy under starvation and ATG5 was first proved to be a target of miR-30b. In summary, we identified HNF1A-AS1-miR-30b axis as a key regulator in hepatocarcinogenesis, which may be promising biomarkers and therapeutic targets in the future.

Keywords: Autophagy; HNF1A-AS1; Hepatocellular carcinoma; Oncogene; miR-30b.

MeSH terms

  • Autophagy / genetics*
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / pathology
  • Gene Expression Regulation, Neoplastic / genetics
  • Hepatocyte Nuclear Factor 1-alpha / genetics*
  • Humans
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / pathology
  • MicroRNAs / genetics*
  • Oncogenes / genetics
  • Promoter Regions, Genetic
  • RNA, Long Noncoding / genetics*
  • Tumor Cells, Cultured

Substances

  • HNF1A protein, human
  • Hepatocyte Nuclear Factor 1-alpha
  • MIRN30b microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding