LncRNA LINC01057 promotes mesenchymal differentiation by activating NF-κB signaling in glioblastoma. (1st February 2021)

• Record Type: Journal Article
• Authors: Tang, Guodong; Luo, Liyun; Zhang, Jianlei; Zhai, Dongfeng; Huang, Danqing; Yin, Jiang; Zhou, Qin; Zhang, Qiong; Zheng, Guopei
• Is Part Of: Cancer letters. Volume 498(2021)
• Page Start: 152
• Page End: 164
• Publication Date: 2021-02-01
• Subjects: Glioblastoma -- LINC01057 -- Mesenchymal transition -- NF-κB signaling -- IKKα protein; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2020.10.047
• Languages: English
• ISSNs: 0304-3835

Abstract

Abstract: Long non-coding RNAs (lncRNAs) have been potentially identified as new diagnostic markers, prognostic factors and therapeutic targets in cancer. The acquisition of a mesenchymal (MES) phenotype in glioblastomas (GBMs) results into therapeutic resistance and poor clinical outcomes. The correlation between lncRNAs and MES differentiation remains elusive. Here, we report that LINC01057 as a lncRNA is overexpressed in GBMs, especially in MES subtype. LINC01057 knockdown suppresses proliferation, invasion and radioresistance of GBM cells in vitro, and tumor growth in vivo . LINC01057 knockdown leads to loss of MES signature in MES subpopulation of GBM cells, but LINC01057 overexpression promotes MES differentiation in proneural (PN) subpopulation. LINC01057 interacts with IKKα and maintains IKKα nucleus localization, leading to effective chromatin accessibility at NF-κB responsive promoters via histone modification and final NF-κB activation. IKKα knockdown disrupts the effect of LINC01057 overexpression on PN to MES transition (PMT). LINC01057 level is negatively correlated with patient prognosis in MES-subtype GBM. Collectively, our findings uncover LINC01057 as a regulator of NF-κB signaling to promote MES differentiation and a potential target for therapeutic intervention for MES-subtype GBM. Highlights: lncRNA LINC01057 overexpressed in GBMs and associated with poor prognosis. LINC01057 maintains the MES phenotype in GBM cells. LINC01057 interacts with IKKα to activate NF-κB signaling. LINC01057 interacts with IKKα to regulates histone modification.