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RNA interference against TMEM97 inhibits cell proliferation, migration, and invasion in glioma cells

Tumour Biol. 2015 Sep;36(10):8231-8. doi: 10.1007/s13277-015-3552-6. Epub 2015 May 23.

Abstract

Gliomas are the most common form of primary brain tumor in the adult central nervous system. Altered expression and prognostic value of transmembrane protein 97 (TMEM97) has been recently reported in different types of human tumors. However, the association of TMEM97and glioma is poorly defined. Here, we reported that TMEM97 was significantly increased in glioma tissues compared to non-tumorous brain tissues. Furthermore, TMEM97 levels were progressively increased with increasing histologic tumor grade in glioma. Higher TMEM97 expression level was correlated with shorter survival time of patients with glioma. Downregulation of TMEM97 through RNA interference inhibited cell proliferation and G1/S transition in two glioma cell lines, U87 and U373. More importantly, TMEM97 silencing induced a significant decrease in the expression of G1/S transition key regulators, cyclin D1, cyclin E, CDK2, and CDK4. Additionally, downregulation of TMEM97 in glioma cells notably repressed cell migration and cell invasion. Further analysis suggested that the decreased invasion was associated with alterations in EMT markers, including E-cadherin, β-catenin, and Twist. Since expression of TMEM97 seems to be associated with the oncogenic potential of glioma, and suppression of its expression can inhibit cancer cell growth and metastasis, TMEM97 may be a potential therapeutic target in human glioma.

Keywords: Cell cycle; Glioma; Invasion; Proliferation; TMEM97.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Apoptosis
  • Blotting, Western
  • Brain / metabolism*
  • Brain Neoplasms / genetics
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology*
  • Case-Control Studies
  • Cell Cycle
  • Cell Movement*
  • Cell Proliferation*
  • Glioma / genetics
  • Glioma / metabolism
  • Glioma / pathology*
  • Humans
  • Immunoenzyme Techniques
  • Membrane Proteins / antagonists & inhibitors
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Neoplasm Grading
  • Neoplasm Invasiveness
  • Prognosis
  • RNA, Small Interfering / genetics*
  • Tumor Cells, Cultured

Substances

  • Membrane Proteins
  • RNA, Small Interfering
  • TMEM97 protein, human