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TGF-β-activated lncRNA LINC00115 is a critical regulator of glioma stem-like cell tumorigenicity.
EMBO Reports ( IF 6.5 ) Pub Date : 2019-10-10 , DOI: 10.15252/embr.201948170 Jianming Tang 1 , Bo Yu 1 , Yanxin Li 2 , Weiwei Zhang 1 , Angel A Alvarez 3 , Bo Hu 3 , Shi-Yuan Cheng 3 , Haizhong Feng 1
EMBO Reports ( IF 6.5 ) Pub Date : 2019-10-10 , DOI: 10.15252/embr.201948170 Jianming Tang 1 , Bo Yu 1 , Yanxin Li 2 , Weiwei Zhang 1 , Angel A Alvarez 3 , Bo Hu 3 , Shi-Yuan Cheng 3 , Haizhong Feng 1
Affiliation
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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.
中文翻译：
TGF-β激活的lncRNA LINC00115是神经胶质瘤干样细胞致瘤性的关键调节剂。
长的非编码RNA（lncRNA）是癌症的关键调节因子。然而，尚不清楚lncRNAs是否参与TGF-β调节的致瘤性。在这里，我们确定TGF-β激活的lncRNA LINC00115是神经胶质瘤干样细胞（GSC）自我更新和致瘤性的关键调节剂。LINC00115被TGF-β上调，起miRNA海绵的作用，并通过与miR-200s竞争性结合而上调ZEB1，从而增强ZEB1信号传导和GSC自我更新。LINC00115还通过阻止miR-200s与ZNF596的5'-UTR结合来促进ZNF596转录，从而导致ZNF596 / EZH2 / STAT3信号传导增强和GBM肿瘤生长。通过遗传方法或小分子抑制剂抑制EZH2可显着抑制LINC00115驱动的GSC自我更新和致瘤性。此外，LINC00115在GBM中得到了高度表达，LINC00115表达或与ZEB1或ZNF596相关的共表达可预示临床GBM生存。我们的工作定义了LINC00115在GSC自我更新和致瘤性中的关键作用，并建议LINC00115作为GBM治疗的潜在靶标。
更新日期：2019-12-05
中文翻译：
TGF-β激活的lncRNA LINC00115是神经胶质瘤干样细胞致瘤性的关键调节剂。
长的非编码RNA（lncRNA）是癌症的关键调节因子。然而，尚不清楚lncRNAs是否参与TGF-β调节的致瘤性。在这里，我们确定TGF-β激活的lncRNA LINC00115是神经胶质瘤干样细胞（GSC）自我更新和致瘤性的关键调节剂。LINC00115被TGF-β上调，起miRNA海绵的作用，并通过与miR-200s竞争性结合而上调ZEB1，从而增强ZEB1信号传导和GSC自我更新。LINC00115还通过阻止miR-200s与ZNF596的5'-UTR结合来促进ZNF596转录，从而导致ZNF596 / EZH2 / STAT3信号传导增强和GBM肿瘤生长。通过遗传方法或小分子抑制剂抑制EZH2可显着抑制LINC00115驱动的GSC自我更新和致瘤性。此外，LINC00115在GBM中得到了高度表达，LINC00115表达或与ZEB1或ZNF596相关的共表达可预示临床GBM生存。我们的工作定义了LINC00115在GSC自我更新和致瘤性中的关键作用，并建议LINC00115作为GBM治疗的潜在靶标。
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