microRNA-501-5p promotes cell proliferation and migration in gastric cancer by downregulating LPAR1

J Cell Biochem. 2020 Feb;121(2):1911-1922. doi: 10.1002/jcb.29426. Epub 2019 Nov 20.

Abstract

In spite of the achievement in treatment, the gastric cancer (GC) mortality still remains high. MicroRNAs (miRNAs) are a group of small noncoding RNAs that play a crucial part in tumor progression. In this study, we explored the expression and function of microRNA-501-5p (miR-501-5p) in GC cell lines. Quantitative real-time polymerase chain reaction assay results suggested that miR-501-5p was significantly upregulated in GC tissues and cell lines. And, the Cell Counting Kit-8 colony formation and cell migration assay results showed that the downregulation of miR-501-5p decreased GC cell proliferation and migration. Besides that, we found that GC cell cycle was arrested in G2 phase and cell apoptosis rate was increased by silencing the expression of miR-501-5p in GC cell lines using the flow cytometry. We also found that miR-501-5p could directly target lysophosphatidic acid receptor 1 (LPAR1) and negatively regulate LPAR1 expression in GC cell lines by performing dual-luciferase reporter gene assay and Western blot analysis. And, LPAR1 was significantly downregulated in GC tissues and inversely correlated with miR-501-5p expression. Furthermore, LPAR1 downregulation promoted cell proliferation and migration, which were attenuated by cotransfection of miR-501-5p inhibitor in GC cells. In conclusion, miR-501-5p can promote GC cell proliferation and migration by targeting and downregulating LPAR1. miR-501-5p/LPAR1 may become a potential therapeutic target for GC treatment.

Keywords: LPAR1; gastric cancer; miR-501-5p; migration; proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Cell Movement*
  • Cell Proliferation*
  • Down-Regulation
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • MicroRNAs / genetics*
  • Prognosis
  • Receptors, Lysophosphatidic Acid / genetics
  • Receptors, Lysophosphatidic Acid / metabolism*
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology*
  • Tumor Cells, Cultured

Substances

  • Biomarkers, Tumor
  • LPAR1 protein, human
  • MIRN501 microRNA, human
  • MicroRNAs
  • Receptors, Lysophosphatidic Acid