The role of microRNA-1274a in the tumorigenesis of gastric cancer: accelerating cancer cell proliferation and migration via directly targeting FOXO4

Biochem Biophys Res Commun. 2015 Apr 17;459(4):629-35. doi: 10.1016/j.bbrc.2015.02.160. Epub 2015 Mar 6.

Abstract

MicroRNAs (miRNAs) are a series of 18-25 nucleotides length non-coding RNAs, which play critical roles in tumorigenesis. Previous study has shown that microRNA-1274a (miR-1274a) is upregulated in human gastric cancer. However, its role in gastric cancer progression remains poorly understood. Therefore, the current study was aimed to examine the effect of miR-1274a on gastric cancer cells. We found that miR-1274a was overexpressed in gastric cancer tissues or gastric cancer cells including HGC27, MGC803, AGS, and SGC-7901 by qRT-PCR analysis. Transfection of miR-1274a markedly promoted gastric cancer cells proliferation and migration as well as induced epithelial-mesenchymal transition (EMT) of cancer cells. Our further examination identified FOXO4 as a target of miR-1274a, which did not influence FOXO4 mRNA expression but significantly inhibited FOXO4 protein expression. Moreover, miR-1274a overexpression activated PI3K/Akt signaling and upregulated cyclin D1, MMP-2 and MMP-9 expressions. With tumor xenografts in mice models, we also showed that miR-1274a promoted tumorigenesis of gastric cancer in vivo. In all, our study demonstrated that miR-1274a prompted gastric cancer cells growth and migration through dampening FOXO4 expression thus provided a potential target for human gastric cancer therapy.

Keywords: Epithelial–mesenchymal transition; FOXO4; Gastric cancer; MicroRNA-1274a; Migration; Proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle Proteins
  • Cell Line, Tumor
  • Cell Proliferation*
  • Forkhead Transcription Factors
  • Humans
  • MicroRNAs / physiology*
  • Neoplasm Metastasis*
  • Real-Time Polymerase Chain Reaction
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology*
  • Transcription Factors / genetics*

Substances

  • Cell Cycle Proteins
  • FOXO4 protein, human
  • Forkhead Transcription Factors
  • MIRN1274 microRNA, human
  • MicroRNAs
  • Transcription Factors