Expression analysis and implication of Rab1A in gastrointestinal relevant tumor

Sci Rep. 2019 Sep 16;9(1):13384. doi: 10.1038/s41598-019-49786-7.

Abstract

Gastrointestinal cancers have become increasingly prevalent worldwide. Previous studies have reported an oncogenic function of Rab1A in colorectal cancer and hepatocellular carcinomas via the mTOR pathway. However, the exact role of Rab1A in gastrointestinal cancers remains elusive. We detected significantly higher expression of Rab1A in the gastrointestinal tumor tissues compared to that in other cancer types following an in silico analysis of TGCA and GTEX databases. Furthermore, Rab1A was overexpressed in the gastrointestinal tumor tissues compared to the para-tumor tissues. Although Rab1A expression levels were not associated with the tumor-lymph node-metastasis (TNM) stage, Rab1A overexpression in the tumor tissues of a gastric cancer (GC) cohort was strongly correlated with poor prognosis in the patients. In addition, Rab1A knockdown significantly inhibited the in vitro proliferation and migration abilities of GC cells, as well as the growth of GC xenografts in vivo. Furthermore, a positive correlation was observed between Rab1A expression levels and that of different upstream/downstream mTOR targets. Taken together, Rab1A regulates the PI3K-AKT-mTORC1 pathway through the mTORC1 complex consisting of mTORC1, Rheb and Rab1A, and is a promising therapeutic target in GC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Cell Movement*
  • Cell Proliferation*
  • Gastrointestinal Neoplasms / genetics
  • Gastrointestinal Neoplasms / metabolism
  • Gastrointestinal Neoplasms / pathology*
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Lymphatic Metastasis
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Prognosis
  • Survival Rate
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays
  • rab1 GTP-Binding Proteins / genetics
  • rab1 GTP-Binding Proteins / metabolism*

Substances

  • Biomarkers, Tumor
  • RAB1A protein, human
  • rab1 GTP-Binding Proteins