TGF-β-activated lncRNA LINC00115 is a critical regulator of glioma stem-like cell tumorigenicity

Jianming Tang, Bo Yu, Yanxin Li, Weiwei Zhang, Angel A. Alvarez, Bo Hu, Shi Yuan Cheng, Haizhong Feng*

*Corresponding author for this work

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Long non-coding RNAs (lncRNAs) are critical regulators in cancer. However, the involvement of lncRNAs in TGF-β-regulated tumorigenicity is still unclear. Here, we identify TGF-β-activated lncRNA LINC00115 as a critical regulator of glioma stem-like cell (GSC) self-renewal and tumorigenicity. LINC00115 is upregulated by TGF-β, acts as a miRNA sponge, and upregulates ZEB1 by competitively binding of miR-200s, thereby enhancing ZEB1 signaling and GSC self-renewal. LINC00115 also promotes ZNF596 transcription by preventing binding of miR-200s to the 5′-UTR of ZNF596, resulting in augmented ZNF596/EZH2/STAT3 signaling and GBM tumor growth. Inhibition of EZH2 by genetic approaches or a small molecular inhibitor markedly suppresses LINC00115-driven GSC self-renewal and tumorigenicity. Moreover, LINC00115 is highly expressed in GBM, and LINC00115 expression or correlated co-expression with ZEB1 or ZNF596 is prognostic for clinical GBM survival. Our work defines a critical role of LINC00115 in GSC self-renewal and tumorigenicity, and suggests LINC00115 as a potential target for GBM treatment.

Original languageEnglish (US)
Article numbere48170
JournalEMBO Reports
Volume20
Issue number12
DOIs
StatePublished - Dec 5 2019

Keywords

  • EZH2
  • ZEB1
  • ZNF596
  • glioma stem-like cell
  • lncRNA LINC00115

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics

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