Targeting strategies on miRNA-21 and PDCD4 for glioblastoma

Arch Biochem Biophys. 2015 Aug 15:580:64-74. doi: 10.1016/j.abb.2015.07.001. Epub 2015 Jul 2.

Abstract

MicroRNAs (miRNAs) are often deregulated in glioblastoma multiforme (GBM). Downregulation of microRNA-21 (miR-21), especially in GBM, is responsible for increased apoptosis, decreased cell proliferation and invasion, increased G0/G1 cell cycle arrest, and reduced chemotherapeutic resistance to doxorubicin. Furthermore, it is a critical regulator of multiple downstream genes and signaling pathways involved in gliomagenesis. Programmed cell death 4 (PDCD4) is critical in mediating apoptosis in GBM, and is downregulated by miR-21, which may mediate the resistance of glioblastoma cells against chemotherapy or radiation via its target genes PDCD4. Evidence is mounting that how alterations of these miRNAs transcription factors provide initiation, maintenance, or progression of tumors. This review will focus on the roles of miRNAs family members (particularly miR-21 and its target gene PDCD4) in tumors like glioblastoma and new targeting strategies, as examples some new targeting therapeutic methods and molecular mechanisms of signal pathways in glioblastoma therapeutics, to give the reader the current trends of approach to target regulation of these miRNA and genes for future glioma therapies.

Keywords: Apoptosis; Glioblastoma; Oncogenes; Resistance; Signaling pathways; miRNA.

Publication types

  • Review

MeSH terms

  • Apoptosis / genetics
  • Apoptosis Regulatory Proteins / genetics*
  • Apoptosis Regulatory Proteins / metabolism
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology
  • Brain Neoplasms / therapy
  • Cell Cycle / genetics
  • Cell Line, Tumor
  • Gene Expression Regulation, Neoplastic*
  • Glioblastoma / genetics*
  • Glioblastoma / metabolism
  • Glioblastoma / pathology
  • Glioblastoma / therapy
  • Humans
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Molecular Targeted Therapy
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA, Messenger / genetics*
  • RNA, Messenger / metabolism
  • RNA-Binding Proteins / genetics*
  • RNA-Binding Proteins / metabolism
  • STAT3 Transcription Factor / genetics
  • STAT3 Transcription Factor / metabolism
  • Signal Transduction

Substances

  • Apoptosis Regulatory Proteins
  • MIRN21 microRNA, human
  • MicroRNAs
  • PDCD4 protein, human
  • RNA, Messenger
  • RNA-Binding Proteins
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt