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.

长非编码RNA（lncRNA）已潜在地被确定为癌症的新诊断标记，预后因素和治疗靶标。胶质母细胞瘤（GBM）中间充质（MES）表型的获得导致治疗耐药性和不良的临床结果。lncRNA与MES分化之间的相关性仍然难以捉摸。在这里，我们报道LINC01057作为lncRNA在GBM中，特别是在MES亚型中过表达。LINC01057抑制基因在体外抑制GBM细胞的增殖，侵袭和放射抗性，并在体内抑制肿瘤的生长。LINC01057敲低导致GBM细胞的MES亚群中的MES签名丢失，但是LINC01057过度表达促进神经元（PN）亚群中的MES分化。LINC01057与IKKα相互作用并维持IKKα核定位，从而通过组蛋白修饰和最终的NF-κB活化，在NF-κB反应性启动子上实现了有效的染色质可及性。IKKα敲低破坏了LINC01057过表达对PN到MES转换（PMT）的影响。LINC01057水平与MES亚型GBM患者的预后呈负相关。总的来说，我们的发现揭示了LINC01057作为NF-κB信号调节剂，可促进MES分化，并可能成为MES亚型GBM的治疗干预目标。