miR-92a-3p promotes the proliferation and invasion of gastric cancer cells by targeting KLF2

J Biol Regul Homeost Agents. 2020 Jul-Aug;34(4):1333-1341. doi: 10.23812/20-209-A.

Abstract

MicroRNAs (miRNAs) have pivotal roles in the initiation and progression of gastric cancer (GC), and miR-92a-3p has been proved to act as an oncogene in multiple malignancies. However, the molecular mechanisms by which miR-92a-3p contributes to GC remain unclear. The differentially expressed miRNAs were screened by GEO dataset, and the association of miR-92a-3p expression with clinicopathological characteristics and prognosis in patients with GC was analyzed by TCGA dataset. The target genes of miR-92a-3p were identified by bioinformatic analysis, and their interaction was confirmed by luciferase reporter assay. MTT, EdU and Transwell assays were conducted to determine the role of miR-92a-3p in GC cells. As a result, it was found that the expression levels of miR-92a-3p were increased in GC tissues and were associated with tumor size, lymph node infiltration and distant metastasis, acting as an independent prognostic factor of poor survival in patients with GC. Restored expression of miR-92a-3p facilitated cell proliferation, DNA synthesis and cell invasion, but its inhibitor reversed these effects. KLF2 was further identified as a direct target of miR-92a-3p, indicating a negative correlation with miR-92a-3p expression and harboring a favorable prognosis in GC. In addition, KLF2 repressed cell proliferation and invasion and attenuated the tumor-promoting effects of miR-92a-3p in GC cells. Altogether, our findings demonstrated that miR-92a-3p promoted the proliferation and invasion of GC cells by targeting KLF2.

Keywords: KLF2; gastric cancer; invasion; miR-92a-3p; proliferation.

MeSH terms

  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kruppel-Like Transcription Factors / genetics
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness
  • Stomach Neoplasms* / genetics

Substances

  • KLF2 protein, human
  • Kruppel-Like Transcription Factors
  • MicroRNAs