MiR-19a promotes epithelial-mesenchymal transition through PI3K/AKT pathway in gastric cancer

World J Gastroenterol. 2015 Apr 21;21(15):4564-73. doi: 10.3748/wjg.v21.i15.4564.

Abstract

Aim: To investigate the mechanism by which miR-19a is up-regulated in gastric cancer (GC), which plays an oncogenic role.

Methods: In the present study, we investigated the role of miR-19a in gastric tissues as well as two GC cell lines. In vivo, we detected the basal expression level of miR-19a using real-time reverse transcription-PCR (RT-PCR), and the relevance between expression of miR-19a and clinicopathological information was analyzed. In vitro, miR-19a was ectopically expressed using overexpression and knock-down strategies.

Results: Overexpression of miR-19a was significantly associated with metastasis of GC and inferior overall prognosis. However, no significant correlation was found between miR-19a expression and other characteristics such as age, gender, tobacco, alcohol or tumor size. Cell proliferation, migration and invasion assays showed that overexpression of miR-19a promoted the proliferation, migration and invasion, and that overexpression of miR-19a promoted the epithelial-mesenchymal transition through activating the PI3K/AKT pathway. Blocking the PI3K/AKT pathway could cancel the effect of miR-19a.

Conclusion: All together, our results suggest that miR-19a could be used as a promising therapeutic target in the treatment of GC.

Keywords: Epithelial-mesenchymal transition; Gastric cancer; MiR-19a; PI3K-AKT.

MeSH terms

  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Epithelial-Mesenchymal Transition*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Humans
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Phosphatidylinositol 3-Kinase / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • RNA Interference
  • Signal Transduction
  • Stomach Neoplasms / enzymology*
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / pathology
  • Transfection
  • Up-Regulation

Substances

  • MIRN19 microRNA, human
  • MicroRNAs
  • Phosphatidylinositol 3-Kinase
  • Proto-Oncogene Proteins c-akt