The novel long non-coding RNA TALNEC2, regulates tumor cell growth and the stemness and radiation response of glioma stem cells

Shlomit Brodie, Hae Kyung Lee, Wei Jiang, Simona Cazacu, Cunli Xiang, Laila M. Poisson, Indrani Datta, Steve Kalkanis, Doron Ginsberg, Chaya Brodie

Research output: Contribution to journalArticlepeer-review

52 Scopus citations

Abstract

Despite advances in novel therapeutic approaches for the treatment of glioblastoma (GBM), the median survival of 12-14 months has not changed significantly. Therefore, there is an imperative need to identify molecular mechanisms that play a role in patient survival. Here, we analyzed the expression and functions of a novel lncRNA, TALNEC2 that was identified using RNA seq of E2F1-regulated lncRNAs. TALNEC2 was localized to the cytosol and its expression was E2F1-regulated and cell-cycle dependent. TALNEC2 was highly expressed in GBM with poor prognosis, in GBM specimens derived from shortterm survivors and in glioma cells and glioma stem cells (GSCs). Silencing of TALNEC2 inhibited cell proliferation and arrested the cells in the G1\S phase of the cell cycle in various cancer cell lines. In addition, silencing of TALNEC2 decreased the self-renewal and mesenchymal transformation of GSCs, increased sensitivity of these cells to radiation and prolonged survival of mice bearing GSC-derived xenografts. Using miRNA array analysis, we identified specific miRNAs that were altered in the silenced cells that were associated with cell-cycle progression, proliferation and mesenchymal transformation. Two of the downregulated miRNAs, miR-21 and miR-191, mediated some of TALNEC2 effects on the stemness and mesenchymal transformation of GSCs. In conclusion, we identified a novel E2F1-regulated lncRNA that is highly expressed in GBM and in tumors from patients of short-term survival. The expression of TALNEC2 is associated with the increased tumorigenic potential of GSCs and their resistance to radiation. We conclude that TALNEC2 is an attractive therapeutic target for the treatment of GBM.

Original languageEnglish
Pages (from-to)31785-31801
Number of pages17
JournalOncotarget
Volume8
Issue number19
DOIs
StatePublished - 9 May 2017

Bibliographical note

Publisher Copyright:
© Brodie et al.

Keywords

  • Glioblastoma
  • Glioma stem cells
  • Long non-cording RNAs
  • Mesenchymal transformation
  • TALNEC2

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