Rab14 Act as Oncogene and Induce Proliferation of Gastric Cancer Cells via AKT Signaling Pathway

PLoS One. 2017 Jan 20;12(1):e0170620. doi: 10.1371/journal.pone.0170620. eCollection 2017.

Abstract

Rab14 is a member of RAS oncogene family, and its dysfunction has been reported to be involved in various types of human cancer. However, its expression and function were still unclear in gastric cancer. The aim of this study was to investigate the function and mechanism of Rab14 in gastric cancer cell lines. Quantitative real-time PCR (qRT-PCR) was performed in 17 gastric adenocarcinoma tissues and 4 cell lines to detect the expression of Rab14. 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-tetrazolium bromide (MTT), colony formation and flow cytometry assays were employed to determine the proliferative ability, cell cycle transition and apoptosis in vitro in BGC-823 or SGC-7901 cells. Western blot was performed to investigate the pathways and mechanism of Rab14 regulation. In this study, we show that Rab14 presents a significant up-regulated expression among the paired tissue samples and cell lines in gastric cancer. When we overexpressed Rab14 in SGC-7901 cells or silenced Rab14 in BGC-823 cells, we found that Rab14 could modify cell growth, cell cycle or apoptosis, which accompanied with an obvious regulation of CCND1, CDK2 and BAX involving in AKT signaling pathway. In conclusion, this study provides a new evidence on that Rab14 functions as a novel tumor oncogene and could be a potential therapeutic target in gastric cancer.

MeSH terms

  • Adenocarcinoma / physiopathology*
  • Apoptosis / physiology
  • Blotting, Western
  • Cell Cycle / physiology
  • Cell Line, Tumor
  • Cell Proliferation / physiology*
  • Flow Cytometry
  • Gene Expression Regulation, Neoplastic / physiology
  • Humans
  • Oncogene Protein v-akt / physiology*
  • Oncogenes / physiology*
  • Real-Time Polymerase Chain Reaction
  • Signal Transduction / physiology*
  • Stomach Neoplasms / physiopathology*
  • Up-Regulation
  • rab GTP-Binding Proteins / physiology*

Substances

  • Oncogene Protein v-akt
  • Rab14 protein, human
  • rab GTP-Binding Proteins

Grants and funding

This work was funded by Biomedical Sharing Platform Project of Xi'an Jiaotong University (2015FWPT-14), Shaanxi Province Science and Technology Projects (2014D75), National Natural Science Foundation of China (81660492), China Postdoctoral Science Foundation (2016M602801), the Fundamental Research Funds for the Central Universities (0811/1191320073). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.