MiR-34a suppresses the proliferation and invasion of gastric cancer by modulating PDL1 in the immune microenvironment

Mol Cell Probes. 2020 Oct:53:101601. doi: 10.1016/j.mcp.2020.101601. Epub 2020 May 20.

Abstract

Objectives: As one of the most serious malignant carcinomas that threaten the life of sufferers constantly, gastric cancer has attracted a lot of interest among researchers. miR-34a, a member of hundreds of microRNAs (miRNAs), has been elucidated to exert a suppressive role in gastric cancer tumorgenesis based on previous extensive studies. Our study was performed with the aim to explore the functional effects of miR-34a and its predictive target programmed death ligand 1 (PDL1) in gastric cancer development.

Methods: We employed reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western Blot analysis to investigate the regulatory effect of miR-34a on PDL1 mRNA and the corresponding protein expression. The CCK-8 and colony formation assays were used to validate the influence of the combination of miR-34a and PDL1 on the proliferation of gastric tumor cells. Meanwhile, the migration and invasion of gastric tumor cells were measured using Transwell assay.

Results: PDL1 was targeted and negatively modulated by miR-34a. In addition, the re-expression of miR-34a suppressed the proliferation as well as the migration and invasion of gastric tumor cells, whereas PDL1 reduced the aforementioned inhibitory effect.

Conclusions: PDL1 is the downstream gene of miR-34a, which can act as an anti-oncogene in gastric cancer. The miR-34a/PDL1 axis might provide a promising anticancer therapeutic approach for the clinical diagnosis, treatment, and prognosis of gastric cancer.

Keywords: Gastric cancer; Immunotherapy; PDL1; miR-34a.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • B7-H1 Antigen / genetics*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Down-Regulation*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness
  • Stomach Neoplasms / genetics*
  • Tumor Microenvironment

Substances

  • B7-H1 Antigen
  • CD274 protein, human
  • MIRN34 microRNA, human
  • MicroRNAs