Nat Commun:中科院范祖森研究组揭示癌症干细胞所需的lncRNA

2016年12月1日，国际学术权威刊物自然出版集团旗下子刊《Nature communications》杂志在线发表了中国科学院生物物理所的范祖森研究员题为“LncBRM initiates YAP1 signalling activation to drive self-renewal of liver cancer stem cells”的研究论文。研究人员鉴定了一种驱动肝癌干细胞自我更新的长非编码RNA(lncRNA)。

研究显示，lncBRM在肝癌干细胞和HCC肿瘤中高度表达，而且肝癌干细胞的自我更新和HCC肿瘤的起始需要LncBRM。在肝癌干细胞中，lncBRM与BRM相互关联并启动BRG1/BRM开关，BRG1所在的BAF复合物激活YAP1信号通路，促进肝癌干细胞的自我更新。

进一步研究表明，lncBRM和YAP1信号靶标的表达水平与HCC患者的肿瘤严重程度正相关。lncBRM和YAP1信号通路的靶标可以作为生物指标用于诊断和预后，也可以帮助人们开发对抗HCC的新治疗药物。

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原文摘要：

Liver cancer stem cells (CSCs) may contribute to the high rate of recurrence and heterogeneity of hepatocellular carcinoma (HCC). However, the biology of hepatic CSCs remains largely undefined. Through analysis of transcriptome microarray data, we identify a long noncoding RNA (lncRNA) called lncBRM, which is highly expressed in liver CSCs and HCC tumours. LncBRM is required for the self-renewal maintenance of liver CSCs and tumour initiation. In liver CSCs, lncBRMassociates with BRM to initiate the BRG1/BRM switch and the BRG1-embedded BAF complex triggers activation of YAP1 signalling. Moreover, expression levels of lncBRM together with YAP1 signalling targets are positively correlated with tumour severity of HCC patients. Therefore,lncBRM and YAP1 signalling may serve as biomarkers for diagnosis and potential drug targets for HCC.