Long noncoding RNA MACC1-AS1 promotes the stemness of hepatocellular carcinoma cells by antagonizing miR-145

J Int Med Res. 2020 Apr;48(4):300060520920411. doi: 10.1177/0300060520920411.

Abstract

Objectives: This work aimed to investigate the roles of long noncoding (lnc)RNA MACC1-AS1 (MACC1 antisense RNA 1) in progression of hepatocellular carcinoma (HCC).

Methods: Real-time quantitative PCR, western blot, spheroid formation, aldehyde dehydrogenase isoform 1 (ALDH1) activity analysis, luciferase reporter assay, and RNA pull-down analysis were used to examine MACC1-AS1–mediated effects on HCC cell stemness.

Results: MACC1-AS1 was highly expressed in HCC tissues and cells. MACC1-AS1 positively regulated the expression of stemness master regulators and inhibited spheroid-forming ability and ALDH1 activity. Furthermore, MACC1-AS1 promoted the stemness of HCC cells by antagonizing microRNA (miR)-145 activity. Overexpression of miR-145 also attenuated HCC cell stemness.

Conclusions: This work revealed a novel MACC1-AS1/miR-145 axis that regulates the stemness of HCC cells.

Keywords: LncRNA; MACC1-AS1; cancer stem cell; hepatocellular carcinoma; miR-145; stemness.

MeSH terms

  • Adult
  • Aged
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Neoplastic Stem Cells / metabolism
  • Neoplastic Stem Cells / pathology
  • RNA, Antisense / genetics
  • RNA, Long Noncoding / genetics
  • Trans-Activators / genetics*
  • Trans-Activators / metabolism

Substances

  • MACC1 protein, human
  • MIRN145 microRNA, human
  • MicroRNAs
  • RNA, Antisense
  • RNA, Long Noncoding
  • Trans-Activators