Knockdown of Rab9 Suppresses the Progression of Gastric Cancer Through Regulation of Akt Signaling Pathway

Technol Cancer Res Treat. 2020 Jan-Dec:19:1533033820915958. doi: 10.1177/1533033820915958.

Abstract

Rabs have been reported to be involved in the carcinogenesis process and in the progression of cancer. However, it is unclear whether or not Rab9 is associated with the development of cancer. In the present study, we aimed to investigate the role of Rab9 in the biological functions of gastric cancer cells. The gastric cancer cell lines AGS and MKN45 were transfected with siRNA-Rab9 to block the expression of Rab9. The cell viability, proliferation, migration, invasion, and apoptosis were examined using Cell Count Kit-8, colony formation, wound healing, Transwell, and flow cytometry assays, respectively. Our data showed that silencing of Rab9 significantly inhibited the viability, proliferation, migration, and invasion abilities of AGS and MKN45 cells. Moreover, transfection with siRab9 promoted the rate of apoptosis in AGS and MKN45 cells through regulating the Bcl-2-Bax axis and the Caspase cascade. We also found that silencing of Rab9 inhibited activation of the Akt signaling pathway by downregulating the phosphorylation level of Akt. In conclusion, our data suggest that Rab9 plays an oncogenic role in the progression of gastric cancer, providing a potential target for the treatment of gastric cancer.

Keywords: Akt signaling pathway; Rab9; gastric cancer; invasion; proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / physiology
  • Cell Line, Tumor
  • Cell Movement / physiology
  • Cell Proliferation / physiology
  • Disease Progression
  • Gene Knockdown Techniques / methods
  • Humans
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Signal Transduction
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / pathology
  • rab GTP-Binding Proteins / deficiency
  • rab GTP-Binding Proteins / genetics
  • rab GTP-Binding Proteins / metabolism*

Substances

  • BCL2 protein, human
  • Proto-Oncogene Proteins c-bcl-2
  • Proto-Oncogene Proteins c-akt
  • RAB9A protein, human
  • rab GTP-Binding Proteins