MiR-449c inhibits gastric carcinoma growth

Life Sci. 2015 Sep 15:137:14-9. doi: 10.1016/j.lfs.2015.06.020. Epub 2015 Jul 2.

Abstract

Aims: Gastric carcinoma (GC) is among the leading causes of cancer-related deaths in China. Growing evidence indicates that dysregulation of miRNAs contributes to GC development. Although it has been shown that miR-449c acts as a tumor suppressor in lung cancer, the role of miR-449c in GC remains unclear.

Main methods: Here, we analyzed miR-449c levels in GC tissues and cell lines by RT-qPCR. We also overexpressed and inhibited miR-449c by transfecting miRNA mimics and antisense oligonucleotides (ASO), respectively. Cell growth was analyzed by MTT assay, and cell apoptosis was evaluated by FACS analysis. MiR-449c target genes were predicted using bioinformatics algorithms and confirmed by a dual luciferase reporter assay.

Key findings: We detected lower miR-449c levels in GC tissues; the low miR-449c levels correlated with low survival rate. Overexpression of miR-449c inhibited cell growth and promoted apoptosis, while depletion of miR-449c increased cell growth and suppressed apoptosis. Moreover, the 3' UTR of MET, an oncogene that activates tumor cell growth, appeared to be targeted by miR-449c.

Significance: Together, we showed that the reduced miR-449c levels in GC tissues promote GC growth, which possibly contributes to the low survival rate of GC patients. Mechanistically, miR-449c may target MET to suppress GC cell growth.

Keywords: Apoptosis; Gastric carcinoma (GC); Growth; MET; MicroRNAs (miRNA); miR-449c.

MeSH terms

  • Apoptosis / genetics
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / biosynthesis
  • MicroRNAs / genetics*
  • Oligonucleotides, Antisense / pharmacology
  • Proto-Oncogene Proteins c-met / metabolism
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / pathology*
  • Survival Rate

Substances

  • MIRN449 microRNA, human
  • MicroRNAs
  • Oligonucleotides, Antisense
  • MET protein, human
  • Proto-Oncogene Proteins c-met