MicroRNA-195 inhibits human gastric cancer by directly targeting basic fibroblast growth factor

Clin Transl Oncol. 2017 Nov;19(11):1320-1328. doi: 10.1007/s12094-017-1668-4. Epub 2017 May 12.

Abstract

Purpose: Gastric cancer (GC) is one of the fatal malignancies worldwide with high occurrences but poor outcomes. bFGF has been shown to play significant roles in GC. Yet, whether bFGF affects the development of GC is less studied.

Methods: MicroRNA assays, real-time PCR, and western blot were conducted for expression analysis of miR-195-5p and basic fibroblast growth factor (bFGF). Luciferase activity was measured with mutated bFGF 3'-UTR sequence at the 3' end of the luciferase gene. Two GC cell lines, SNU-1 and KATO-3 overexpressing miR-195-5p and bFGF were subjected to wound healing assay and transwell invasion assay. Mouse GC xenograft model was established and subjected to tumor size analysis.

Results: Expression levels of miR-195-5p and bFGF showed negative correlation in human GC tissues. MiR-195-5p directly targeted bFGF 3'-UTR as demonstrated by luciferase activity assay. MiR-195-5p, through downregulating bFGF, inhibited the migration and invasion of SNU-1 and KATO-3 cells, as well as tumorigenesis in a xenograft mouse model, which could be restored by re-introduction of bFGF.

Conclusions: MiR-195-5p inhibits tumorigenesis of GC through suppressing bFGF, which supports both miR-195-5p and bFGF as potential therapeutic targets in the treatment of GC.

Keywords: Gastric cancer; Invasion; bFGF; miR-195-5p; miRNAs.

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology*
  • Animals
  • Apoptosis*
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Cell Movement
  • Cell Proliferation
  • Female
  • Fibroblast Growth Factor 2 / genetics
  • Fibroblast Growth Factor 2 / metabolism*
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Male
  • Mice
  • Mice, SCID
  • MicroRNAs / genetics*
  • Middle Aged
  • Prognosis
  • Signal Transduction
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology*
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays

Substances

  • Biomarkers, Tumor
  • MIRN195 microRNA, human
  • MicroRNAs
  • Fibroblast Growth Factor 2