Knockdown of TMEM45A inhibits the proliferation, migration and invasion of glioma cells

Int J Clin Exp Pathol. 2015 Oct 1;8(10):12657-67. eCollection 2015.

Abstract

Gliomas are the most common and aggressive type of primary adult brain tumor. Although high expression and prognostic value of TMEM45A has been recently reported in various types of human tumors, the association of TMEM45A expression and glioma is still unknown. Here, we reported that TMEM45A was significantly overexpressed in glioma tissues compared to non-tumorous brain tissues. Furthermore, TMEM45A mRNA levels were gradually increased with the increasing severity of histological grade of glioma. Moreover, high TMEM45A expression level was correlated with short survival time of glioma patients. Down-regulation of TMEM45A in two glioma cell lines, U251 and U373 by transected with TMEM45A siRNA resulted in a significant reduction of cell proliferation and G1-phase arrest. Additionally, we found that suppressing of TMEM45A expression in glioma cells remarkably suppressed cell migration and cell invasion. More importantly, TMEM45A siRNA treatment significantly down-regulated the proteins promoting cell cycles transition (Cyclin D1, CDK4 and PCNA) and cell invasion (MMP-2 and MMP-9), which indicted a possible mechanism underlying its functions on glioma. In summary, our study suggests that TMEM45A may work as an oncogene and a new effective therapeutic target for glioma treatment.

Keywords: TMEM45A; glioma; invasion; proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain Neoplasms / genetics
  • Brain Neoplasms / mortality
  • Brain Neoplasms / pathology*
  • Cell Line, Tumor
  • Cell Movement*
  • Cell Proliferation*
  • Gene Knockdown Techniques
  • Glioma / genetics
  • Glioma / mortality
  • Glioma / pathology*
  • Humans
  • Immunoblotting
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Neoplasm Invasiveness / genetics
  • Polymerase Chain Reaction

Substances

  • Membrane Proteins
  • TMEM45A protein, human