Long non-coding RNA PVT1 promotes autophagy as ceRNA to target ATG3 by sponging microRNA-365 in hepatocellular carcinoma

Gene. 2019 May 20:697:94-102. doi: 10.1016/j.gene.2019.02.036. Epub 2019 Feb 20.

Abstract

The pathogenesis and the underlying mechanisms of hepatocellular carcinoma (HCC) remain unclear. LncRNA plasmacytoma variant translocation 1 (PVT1) is an oncogene in a variety of cancers. The role of PVT1 in HCC progression is not completely understood. In the present study, we conducted a series of studies to explore the role of PVT1 on autophagy in HCC cells. Our study found PVT1 levels were markedly up-regulated in the corresponding HCC tissues. Importantly, we found that PVT1 could facilitate cell autophagy in HCC cells. Then, we confirmed that the effect of PVT1 promoting autophagy was dependent on regulating ATG3 expression. Further investigations revealed that PVT1 could upregulate autophagy-related gene 3 (ATG3) expression by acting as an endogenous sponge of miR-365, which was an inhibitor gene on ATG3 protein by targeting 3'UTR of ATG3 mRNA. Moreover, rescue assays indicated that the effect of PVT1 on autophagy of HCC cells were dependent on miR-365. In conclusion, our study demonstrated PVT1 might be a key regulator participating in autophagy in HCC cells. We proved that PVT1 could promote autophagy as ceRNA by targeting miR-365.

Keywords: ATG3; Autophagy; HCC; PVT1; miR-365.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Autophagy / genetics
  • Autophagy-Related Proteins / genetics*
  • Autophagy-Related Proteins / metabolism
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology
  • Cell Line, Tumor
  • Cell Proliferation / physiology
  • Disease Progression
  • Female
  • Humans
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology
  • Male
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Middle Aged
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Ubiquitin-Conjugating Enzymes / genetics*
  • Ubiquitin-Conjugating Enzymes / metabolism
  • Up-Regulation

Substances

  • Autophagy-Related Proteins
  • MIRN365 microRNA, human
  • MicroRNAs
  • PVT1 long-non-coding RNA, human
  • RNA, Long Noncoding
  • RNA, Messenger
  • Ubiquitin-Conjugating Enzymes
  • ATG3 protein, human