High expression of RAB43 predicts poor prognosis and is associated with epithelial-mesenchymal transition in gliomas

Oncol Rep. 2017 Feb;37(2):903-912. doi: 10.3892/or.2017.5349. Epub 2017 Jan 3.

Abstract

The Ras-related GTP-binding protein (RAB) family plays an important role in regulating signal transduction and cellular processes including vesicle transport, cytoskeleton formation and membrane trafficking. More recently, several RAB members have been reported to promote tumorigenesis in many types of cancers. However, the clinical significance and potential function of RAB43 in gliomas remain unclear. Herein, we found that RAB43 was upregulated and positively correlated with the grade of progression in glioma patients by in silico analysis and immunohistochemistry (IHC). Patients with high RAB43 displayed worse clinical outcomes in comparison to those with low RAB43. RAB43 was also highly expressed in mesenchymal and G3 subtypes, and isocitrate dehydrogenase 1 (IDH1) wild-type gliomas. Moreover, transcriptomic analyses via Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways revealed that RAB43‑related gene sets were mainly involved in the regulation of cell adhesion and cell migration processes. Further investigation indicated that RAB43 downregulation significantly suppressed the migratory and invasive ability of glioma cells, as well as decreased the expression of epithelial-mesenchymal transition (EMT) markers (N-cadherin, vimentin and Snail). In conclusion, a high level of RAB43 was significantly associated with the malignant phenotypes of gliomas, which suggests that RAB43 may serve as a novel biomarker and a potential therapeutic target for gliomas.

MeSH terms

  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Blotting, Western
  • Brain Neoplasms / genetics
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology*
  • Cell Adhesion
  • Cell Movement
  • Disease Progression
  • Epithelial-Mesenchymal Transition*
  • Female
  • Follow-Up Studies
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Glioma / genetics
  • Glioma / metabolism
  • Glioma / pathology*
  • Humans
  • Immunoenzyme Techniques
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Prognosis
  • Survival Rate
  • Tumor Cells, Cultured
  • rab GTP-Binding Proteins / genetics
  • rab GTP-Binding Proteins / metabolism*

Substances

  • Biomarkers, Tumor
  • rab11 protein
  • rab GTP-Binding Proteins