Targeting SIM2-s decreases glioma cell invasion through mesenchymal--epithelial transition

J Cell Biochem. 2014 Nov;115(11):1900-7. doi: 10.1002/jcb.24859.

Abstract

Glioma is a common primary intracranial carcinoma with high incidence, recurrence, and motility. Single minded homolog 2-short form (SIM2-s), a member of basic helix-loop-helix (bHLH) family, is reported to be expressed in glioma and might play a role in the invasion. In the present study, we investigated the importance of SIM2-s in glioma invasion and further explored the potential mechanisms. We showed that targeting SIM2-s by interference technology could decrease cell adhesion to fibronectin, induce cell aggregation and cytoskeletal changes. Furthermore, we showed that targeting SIM2-s increased the expression of epithelial markers and decreased the expression of mesenchymal markers, that is mesenchymal-epithelial transition (MET). Targeting SIM2-s decreased self-renewal of glioma stem cells by tumor sphere formation assay. Taken together, our results indicated that MET is involved in the inhibition of glioma invasion by targeting SIM2-s, and SIM2-s may be a new gene target.

Keywords: GLIOMA; INVASION; MET; SIM2-s.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Basic Helix-Loop-Helix Transcription Factors / antagonists & inhibitors*
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Brain Neoplasms / genetics
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology*
  • Cell Adhesion
  • Cell Line, Tumor
  • Cell Movement
  • Epithelial-Mesenchymal Transition / drug effects*
  • Fibronectins / metabolism
  • Gene Expression Regulation, Neoplastic / drug effects
  • Glioma / genetics
  • Glioma / metabolism
  • Glioma / pathology*
  • Humans
  • RNA, Small Interfering / pharmacology*

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Fibronectins
  • RNA, Small Interfering
  • SIM2 protein, human