Rab25 upregulation correlates with the proliferation, migration, and invasion of renal cell carcinoma

Biochem Biophys Res Commun. 2015 Mar 20;458(4):745-50. doi: 10.1016/j.bbrc.2015.01.144. Epub 2015 Feb 14.

Abstract

Renal cell carcinoma (RCC) is a common urological cancer with a poor prognosis. A recent cohort study revealed that the median survival of RCC patients was only 1.5 years and that <10% of the patients in the study survived up to 5 years. In tumor development, Rab GTPase are known to play potential roles such as regulation of cell proliferation, migration, invasion, communication, and drug resistance in multiple tumors. However, the correlation between Rabs expression and the occurrence, development, and metastasis of RCC remains unclear. In this study, we analyzed the transcriptional levels of 52 Rab GTPases in RCC patients. Our results showed that high levels of Rab25 expression were significantly correlated with RCC invasion classification (P < 0.01), lymph-node metastasis (P < 0.001), and pathological stage (P < 0.01). Conversely, in 786-O and A-498 cells, knocking down Rab25 protein expression inhibited cell proliferation, migration, and invasion. Our results also demonstrated that Rab25 is a target gene of let-7d, and further suggested that Rab25 upregulation in RCC is due to diminished expression of let-7d. These findings indicate that Rab25 might be a novel candidate molecule involved in RCC development, thus identifying a potential biological therapeutic target for RCC.

Keywords: Invasion; Let-7d; Migration; Proliferation; Rab25; Renal cell carcinoma.

MeSH terms

  • Carcinoma, Renal Cell / genetics*
  • Carcinoma, Renal Cell / pathology*
  • Cell Line, Tumor
  • Cell Proliferation
  • Cohort Studies
  • Humans
  • Kidney / metabolism
  • Kidney / pathology*
  • Kidney Neoplasms / genetics*
  • Kidney Neoplasms / pathology*
  • Lymph Nodes / metabolism
  • Lymph Nodes / pathology
  • Lymphatic Metastasis / genetics
  • Lymphatic Metastasis / pathology
  • MicroRNAs / genetics
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology
  • Up-Regulation*
  • rab GTP-Binding Proteins / genetics*

Substances

  • MicroRNAs
  • Rab25 protein, human
  • mirnlet7 microRNA, human
  • rab GTP-Binding Proteins