LncSox4 promotes the self-renewal of liver tumour-initiating cells through Stat3-mediated Sox4 expression.
LncSox4 promotes the self-renewal of liver tumour-initiating cells through Stat3-mediated Sox4 expression.
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LncSox4通过Stat3介导的Sox4表达促进肝肿瘤起始细胞的自我更新
DOI：
10.1038/ncomms12598
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发表时间：
2016-08-24
影响因子：
16.6
通讯作者：
Gao YF
中科院分区：
文献类型：
--
作者：
Chen ZZ;Huang L;Wu YH;Zhai WJ;Zhu PP;Gao YF
肝癌在患者中有无症状发展的趋势，因此大多数患者在后期被诊断出来。越来越多的证据表明，肝肿瘤起始细胞（TIC）是肝癌发生和复发的原因。然而，肝脏TIC自我更新的分子机制知之甚少。在这里，我们发现，一个长的非编码RNA（lncRNA）称为LncSox 4是高表达的肝细胞癌（HCC）组织和肝TIC。我们发现LncSox 4是肝脏TIC自我更新和肿瘤发生所必需的。LncSox 4与Stat3相互作用并将Stat3募集到Sox 4启动子以启动Sox 4的表达，Sox 4在肝TIC中高度表达并且是肝TIC自我更新所需的。Sox 4的表达水平与HCC的发生、临床严重程度及预后相关。总之，我们发现LncSox 4在肝脏TIC中高度表达，并且是其自我更新所必需的。
Liver cancer has a tendency to develop asymptomatically in patients, so most patients are diagnosed at a later stage. Accumulating evidence implicates that liver tumour-initiating cells (TICs) as being responsible for liver cancer initiation and recurrence. However, the molecular mechanism of liver TIC self-renewal is poorly understood. Here we discover that a long noncoding RNA (lncRNA) termed LncSox4 is highly expressed in hepatocellular carcinoma (HCC) tissues and in liver TICs. We find that LncSox4 is required for liver TIC self-renewal and tumour initiation. LncSox4 interacts with and recruits Stat3 to the Sox4 promoter to initiate the expression of Sox4, which is highly expressed in liver TICs and required for liver TIC self-renewal. The expression level of Sox4 correlates with HCC development, clinical severity and prognosis of patients. Altogether, we find that LncSox4 is highly expressed in liver TICs and is required for their self-renewal.