MiR-513b-5p represses autophagy during the malignant progression of hepatocellular carcinoma by targeting PIK3R3

Aging (Albany NY). 2021 Jun 13;13(12):16072-16087. doi: 10.18632/aging.203135. Epub 2021 Jun 13.

Abstract

Hepatocellular carcinoma (HCC) serves as a prevailing global malignancy with severe mortality and extremely unsatisfactory prognosis, in which autophagy is a fundamental process in liver cancer pathogenesis, but the mechanisms are poorly understood. MicroRNAs (miRNAs) serve as a type of well-recognized non-coding regulators and contribute to the modulation of liver cancer development, from the aspects of diagnosis, progression, and therapy. Here, we aimed to investigate the function of hsa_microRNA-513b-5p (miR-513b-5p) in regulating autophagy during HCC progression. Specifically, our data showed that miR-513b-5p mimic reduced the LC3-II and beclin1 expression but enhanced p62 expression in HCC cells. MiR-513b-5p repressed liver cancer cell proliferation, migration/invasion, and induced apoptosis in vitro. Crucially, miR-513b-5p attenuated tumor growth of liver cancer cells in vivo. In the mechanical investigation, we identified that PIK3R3 mRNA 3'UTR was targeted by miR-513b-5p and miR-513b-5p suppressed PIK3R3 expression. PIK3R3 overexpression partly reversed miR-513b-5p-mediated autophagy, proliferation, and apoptosis of liver cancer cells. Consequently, we concluded that miR-513b-5p repressed autophagy during the malignant progression of HCC by targeting PIK3R3. MiR-513b-5p may be applied as a therapeutic target for HCC.

Keywords: PIK3R3; autophagy; hepatocellular carcinoma; miR-513b-5p; progression.

MeSH terms

  • Adenine / analogs & derivatives
  • Adenine / pharmacology
  • Apoptosis / genetics
  • Autophagy*
  • Base Sequence
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / pathology*
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Disease Progression*
  • Humans
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / pathology*
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neoplasm Invasiveness
  • Phosphatidylinositol 3-Kinases / metabolism*

Substances

  • MIRN513A1 microRNA, human
  • MicroRNAs
  • 3-methyladenine
  • PIK3R3 protein, human
  • Adenine