MicroRNA-187 promotes growth and metastasis of gastric cancer by inhibiting FOXA2

Oncol Rep. 2017 Mar;37(3):1747-1755. doi: 10.3892/or.2017.5370. Epub 2017 Jan 16.

Abstract

MicroRNAs (miRNAs) play an active role in the pathogenesis of gastric cancer. The expression and biological function for miR-187 in gastric cancer remains unknow. In the present study, we demonstrated that miR-187 expression was increased in gastric cancer (GC) tissues and cells. Increased expression level of miR-187 was associated with adverse clinical features including tumor size, lymph metastasis and TNM stage, and decreased overall survival and disease-free survival of GC patients. Functionally, overexpression miR-187 could promote while inhibition of miR-187 could suppress, the proliferation, migration and invasion of GC cells in vitro. In vivo experiments showed that overexpression of miR-187 promoted the growth and lung metastasis of SGC-7901 cells in nude mice. Mechanically, we confirmed that FOXA2 was the downstream target of miR-187 in GC cells using luciferase assay, qRT-PCR and western blot analysis. Moreover, overexpression of FOXA2 abrogated the promoting effects of miR-187 overexpression on SGC-7901 cell proliferation, migration and invasion, while inhibition of FOXA2 reversed the inhibitory effects of miR-187 downregulation on these biological functions of AGS cells, suggesting that FOXA2 was a functional mediator of miR-187 in GC. Therefore, this study indicates that miR-187 is potentially a biomarker and treatment target for GC patients.

MeSH terms

  • Aged
  • Animals
  • Apoptosis
  • Blotting, Western
  • Cell Line, Tumor
  • Cell Movement*
  • Cell Proliferation*
  • Female
  • Gastric Mucosa / metabolism
  • Gene Expression Regulation, Neoplastic
  • Hepatocyte Nuclear Factor 3-beta / antagonists & inhibitors
  • Hepatocyte Nuclear Factor 3-beta / genetics
  • Hepatocyte Nuclear Factor 3-beta / metabolism*
  • Humans
  • Lymphatic Metastasis
  • Male
  • Mice
  • Mice, Nude
  • MicroRNAs / genetics*
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stomach / pathology
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology*
  • Xenograft Model Antitumor Assays

Substances

  • FOXA2 protein, human
  • MIRN187 microRNA, human
  • MicroRNAs
  • RNA, Messenger
  • Hepatocyte Nuclear Factor 3-beta