HOXA-AS3 Promotes Proliferation and Migration of Hepatocellular Carcinoma Cells via the miR-455-5p/PD-L1 Axis

J Immunol Res. 2021 Dec 27:2021:9289719. doi: 10.1155/2021/9289719. eCollection 2021.

Abstract

Hepatocellular carcinoma (HCC) is the most prevalent type of hepatic carcinoma. Long noncoding RNAs (lncRNAs) are considered crucial regulators of gene expression; however, their functions in HCC are not well understood. Thus, the present study is aimed at elucidating the functions of the lncRNA HOXA-AS3 in HCC. The functions of the HOXA-AS3/miR-455-5p/programmed death-ligand 1 (PD-L1) axis were investigated in vitro via qRT-PCR and dual-luciferase reporter assays. The effect of HOXA-AS3 expression on tumor growth and metastasis was assessed using a mouse xenograft model. High HOXA-AS3 expression was observed in the HCC cell lines. Furthermore, overexpression of HOXA-AS3 in HCC cells enhanced proliferation, migration, and invasion, regulated the cell cycle, and retarded apoptosis. We also identified an miR-455-5p binding site in HOXA-AS3. By sponging miR-455-5p, HOXA-AS3 increased the expression of PD-L1. Additionally, both the inhibition of PD-L1 and overexpression of miR-455-5p reversed the effects on cell proliferation and invasion triggered by the overexpression of HOXA-AS3. In conclusion, HOXA-AS3 modulated the functions of HCC cells through the miR-455-5p/PD-L1 axis. Therefore, HOXA-AS3 may be a novel therapeutic target for HCC.

MeSH terms

  • Apoptosis / genetics
  • B7-H1 Antigen / genetics*
  • B7-H1 Antigen / metabolism
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / metabolism
  • Cell Cycle / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation
  • Databases, Genetic
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / metabolism
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • RNA Interference
  • RNA, Long Noncoding / genetics*

Substances

  • B7-H1 Antigen
  • CD274 protein, human
  • MIRN455 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding