miR-155 Regulates Glioma Cells Invasion and Chemosensitivity by p38 Isforms In Vitro

J Cell Biochem. 2015 Jul;116(7):1213-21. doi: 10.1002/jcb.25073.

Abstract

The critical role of microRNAs in cancer development has been extensively described. miRNAs are both specific markers and putative therapy targets. miR-155 has been identified to be an oncomiRNA and is highly expressed in several solid cancers, including glioblastoma. In this study, we found that miR-155 is a good potential therapy target. Knockdown of miR-155 sensitizes glioma cells to the chemotherapy of temozolomide (TMZ) by targeting the p38 isoforms mitogen-activated protein kinase 13 [MAPK13, also known as p38 MAPKδ or stress-activated protein kinase 4 (SAPK4)] and MAPK14 (also known as p38 MAPKα). As tumor suppressor genes, MAPK13 and MAPK14 play important roles in lowering the accumulation of reactive oxygen species (ROS), inducing cell apoptosis, and slowing the progression of cancer. Knockdown of miR-155 enhanced the anticancer effect of TMZ on glioma by targeting the MAPK13 and MAPK14-mediated oxidative stress and apoptosis, but did not affect the secretion of MMP2 and MMP9.

Keywords: CHEMOSENSITIVITY; GLIOBLASTOMA; MAPK; REACTIVE OXYGEN SPECIES; TEMOZOLOMIDE; microRNA.

MeSH terms

  • Apoptosis
  • Brain Neoplasms / drug therapy
  • Brain Neoplasms / genetics
  • Brain Neoplasms / pathology*
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Dacarbazine / analogs & derivatives*
  • Dacarbazine / pharmacology
  • Gene Knockdown Techniques
  • Glioblastoma / drug therapy
  • Glioblastoma / genetics
  • Glioblastoma / pathology*
  • Humans
  • In Vitro Techniques
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism*
  • Mitogen-Activated Protein Kinase 13 / genetics
  • Mitogen-Activated Protein Kinase 13 / metabolism
  • Mitogen-Activated Protein Kinase 14 / genetics
  • Mitogen-Activated Protein Kinase 14 / metabolism
  • Oxidative Stress / drug effects
  • Temozolomide

Substances

  • MIRN155 microRNA, human
  • MicroRNAs
  • Dacarbazine
  • Mitogen-Activated Protein Kinase 13
  • Mitogen-Activated Protein Kinase 14
  • Temozolomide