Long intergenic noncoding RNA 00021 promotes glioblastoma temozolomide resistance by epigenetically silencing p21 through Notch pathway

IUBMB Life. 2020 Aug;72(8):1747-1756. doi: 10.1002/iub.2301. Epub 2020 May 24.

Abstract

Increasing findings are suggesting the vital roles of long noncoding RNAs (lncRNAs) in the glioblastoma tumorigenesis. However, whether the novel lncRNA LINC00021 modulates temozolomide (TMZ) resistance of glioblastoma is still unclear. Clinically, lncRNA LINC00021 was significantly up-regulated in glioblastoma, especially the TMZ-resistant tissue and cells, and the LINC00021 overexpression was closely correlated to TMZ resistance and unfavorable prognosis. Functionally, LINC00021 positively promoted the TMZ resistance and reduced apoptosis. Mechanistically, transcription factor E2F1 activated the expression of LINC00021. Moreover, LINC00021 regulated the glioblastoma TMZ resistance through Notch pathway and epigenetically silenced p21 expression via recruiting EZH2. Collectively, present research indicates the critical roles of lncRNA LINC00021 in glioblastoma genesis, providing a novel insight for TMZ resistance in glioblastoma.

Keywords: LINC00021; chemotherapy resistance; glioblastoma; temozolomide.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics*
  • Drug Resistance, Neoplasm / genetics
  • E2F1 Transcription Factor / genetics
  • Enhancer of Zeste Homolog 2 Protein / genetics
  • Epigenesis, Genetic / genetics
  • Gene Expression Regulation, Neoplastic / genetics
  • Glioblastoma / drug therapy*
  • Glioblastoma / genetics
  • Glioblastoma / pathology
  • Humans
  • Mice
  • RNA, Long Noncoding / genetics*
  • Receptors, Notch / genetics
  • Temozolomide / pharmacology*
  • Xenograft Model Antitumor Assays

Substances

  • CDKN2A protein, human
  • Cyclin-Dependent Kinase Inhibitor p16
  • E2F1 Transcription Factor
  • E2F1 protein, human
  • RNA, Long Noncoding
  • Receptors, Notch
  • EZH2 protein, human
  • Enhancer of Zeste Homolog 2 Protein
  • Temozolomide