Long noncoding RNA MALAT1 knockdown reverses chemoresistance to temozolomide via promoting microRNA-101 in glioblastoma

Cancer Med. 2018 Apr;7(4):1404-1415. doi: 10.1002/cam4.1384. Epub 2018 Feb 26.


Glioblastoma (GBM) is the most common and lethal tumor of the central nervous system with highly infiltrative and resistant to chemotherapy. Temozolomide (TMZ) is widely used as the first-line treatment for the therapy of GBM. However, a considerable percentage inherent or acquired resistance in GBM accounts for many treatment failures of the TMZ chemotherapy. Therefore, a deeper understanding of the molecular characteristics underlying TMZ resistance and the identification of novel therapeutic target is urgent. Here, we show that MALAT1 was significantly upregulated in TMZ-resistant GBM cells. On the other hand, MALAT1 knockdown reduces TMZ resistance of GBM cells both in vitro and in vivo by inhibiting cell proliferation and promoting apoptosis. We also show that miR-101 overexpression reduced TMZ resistance of GBM cells and played an antagonistic role compared with MALAT1. Importantly, we demonstrate that MALAT1 promoted the chemoresistance through suppressing miR-101 signaling pathway via directly binding it in GBM cells. In conclusion, our study indicates that knockdown of MALAT1 reverses chemoresistance to TMZ via promoting miR-101 regulatory network in GBM and thus offers a novel prognostic marker and potential target for GBM TMZ-based chemotherapy.

Keywords: Chemoresistance; LncRNA MALAT1; glioblastoma; miR-101; temozolomide.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • DNA Modification Methylases / genetics
  • DNA Repair Enzymes / genetics
  • Disease Models, Animal
  • Drug Resistance, Neoplasm / genetics*
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Gene Knockdown Techniques
  • Genes, Reporter
  • Glioblastoma / genetics*
  • Glioblastoma / pathology
  • Glycogen Synthase Kinase 3 beta / metabolism
  • Heterografts
  • Humans
  • Male
  • Mice
  • MicroRNAs / genetics*
  • RNA Interference*
  • RNA, Long Noncoding / genetics*
  • Temozolomide / pharmacology*
  • Tumor Suppressor Proteins / genetics


  • MALAT1 long non-coding RNA, human
  • MIRN101 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • Tumor Suppressor Proteins
  • DNA Modification Methylases
  • MGMT protein, human
  • Glycogen Synthase Kinase 3 beta
  • DNA Repair Enzymes
  • Temozolomide