Effects of hnRNP A2/B1 Knockdown on Inhibition of Glioblastoma Cell Invasion, Growth and Survival

Mol Neurobiol. 2016 Mar;53(2):1132-1144. doi: 10.1007/s12035-014-9080-3. Epub 2015 Jan 14.

Abstract

Heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNP A2/B1) plays an important role in influence of pre-messenger RNA (pre-mRNA) processing and mRNA metabolism and transportation in cells. Increasing evidence indicates that hnRNP A2/B1 played an important role in development and progression of various human cancers. Forty cases of normal and human glioma tissue samples were analyzed using immunohistochemistry to reveal the expression of hnRNP A2/B1 protein in the samples. Then, knockdown of hnRNP A2/B1 expression induced by RNA interference (RNAi) method was used to analyze the role of hnRNP A2/B1 in glioblastoma cell viability, adhesion, migration, invasion, and chemoresistance for temozolomide (TMZ). The data showed that hnRNP A2/B1 protein was overexpressed in glioma tissue specimens and associated with advanced glioma grades. Knockdown of hnRNP A2/B1 could reduce glioblastoma cell viability, adhesion, migration, invasion, and chemoresistance for TMZ capacity, but induced tumor cells to apoptosis and reactive oxygen species (ROS) generation in glioma U251 and SHG44 cells. Molecularly, hnRNP A2/B1 knockdown reduced expression of phospho-STAT3 and MMP-2. Detection of hnRNP A2/B1 expression may be useful as a biomarker for prediction of glioma progression and knockdown of hnRNP A2/B1 expression as a novel strategy in future control of glioblastoma in clinic.

Keywords: Cell growth; Cell invasion; Glioblastoma; hnRNP A2/B1; shRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology*
  • Cell Adhesion / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Dacarbazine / analogs & derivatives
  • Dacarbazine / pharmacology
  • Drug Resistance, Neoplasm / drug effects
  • Female
  • Gene Knockdown Techniques*
  • Glioblastoma / metabolism
  • Glioblastoma / pathology*
  • Heterogeneous-Nuclear Ribonucleoprotein Group A-B / metabolism*
  • Humans
  • Immunohistochemistry
  • Male
  • Matrix Metalloproteinases / metabolism
  • Middle Aged
  • Neoplasm Invasiveness
  • STAT3 Transcription Factor / metabolism
  • Temozolomide
  • Tumor Stem Cell Assay

Substances

  • Heterogeneous-Nuclear Ribonucleoprotein Group A-B
  • STAT3 Transcription Factor
  • Dacarbazine
  • Matrix Metalloproteinases
  • Temozolomide