A novel, liver-specific long noncoding RNA LINC01093 suppresses HCC progression by interaction with IGF2BP1 to facilitate decay of GLI1 mRNA
A novel, liver-specific long noncoding RNA LINC01093 suppresses HCC progression by interaction with IGF2BP1 to facilitate decay of GLI1 mRNA
复制标题
一种新型肝脏特异性长非编码 RNA LINC01093 通过与 IGF2BP1 相互作用促进 GLI1 mRNA 的衰减来抑制 HCC 进展
DOI：
10.1016/j.canlet.2019.02.033
复制
发表时间：
2019-01-01
期刊：
影响因子：
9.7
通讯作者：
Wang, Hui
中科院分区：
文献类型：
--
作者：
He, Jia;Zuo, Qiaozhu;Wang, Hui
长链非编码RNA（IncRNA）是肝细胞癌（HCC）的新驱动因子，但这种关系与肝癌发生的潜在机制尚不清楚。我们报道了一种新的肝脏特异性lncRNA LINC 01093，它在HCC组织中表现出显著的下调。LINC 01093表达与癌栓和HCC TNM分期呈负相关，并可作为HCC患者的预后预测因子。LINC 01093过表达在体外和体内显著抑制HCC细胞增殖和转移。相反，其敲除促进HCC进展。机制分析表明，LINC 01093直接结合胰岛素样生长因子2 mRNA结合蛋白1（IGF 2BP 1），干扰IGF 2BP 1和神经胶质瘤相关癌基因同源物1（GLI 1）mRNA之间的相互作用。结果是GLI 1 mRNA的降解，进一步影响参与HCC进展的GLI 1下游分子的表达。肝脏富集的lncRNA LINC 01093是HCC患者的一个有希望的预后指标，新鉴定的LINC 01093-IGF 2BP 1-GLI 1轴显示了HCC治疗靶点的潜力。
Long noncoding RNAs (IncRNAs) are implicated as novel drivers in hepatocellular carcinoma (HCC), but the underlying mechanisms of this relationship with hepatocarcinogenesis are unknown. We report a novel, liver-specific lncRNA LINC01093 that shows significant downregulation in HCC tissues. LINC01093 expression is inversely correlated with cancer embolus and HCC TNM stage and as a prognostic predictor for HCC patients. LINC01093 overexpression significantly suppresses HCC cell proliferation and metastasis in vitro and in vivo. Conversely, its knockdown promotes HCC progression. Mechanistic analyses indicate that LINC01093 directly binds insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1), interfering with interaction between IGF2BP1 and glioma-associated oncogene homolog 1 (GLI1) mRNA. The result is degradation of GLI1 mRNA, further affecting expression of GLI1 downstream molecules involved in HCC progression. The liver-enriched lncRNA LINC01093 is a promising prognostic indicator for HCC patients, and the newly identified LINC01093-IGF2BP1-GLI1 axis shows potential for therapeutic targets in HCC.