State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200032, China.
Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Fudan University, Shanghai, 200032, China.
Cancer Lett. 2019 May 28;450:98-109. doi: 10.1016/j.canlet.2019.02.033. Epub 2019 Feb 18.
Long noncoding RNAs (lncRNAs) 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.
长链非编码 RNA（lncRNAs）被认为是肝癌（HCC）的新型驱动因子，但它们与肝癌发生的关系的潜在机制尚不清楚。我们报道了一种新型的肝脏特异性 lncRNA LINC01093，其在 HCC 组织中明显下调。LINC01093 的表达与肝癌栓子和 HCC TNM 分期呈负相关，并可作为 HCC 患者的预后预测因子。LINC01093 的过表达可显著抑制 HCC 细胞的体外和体内增殖和转移。相反，其敲低促进 HCC 进展。机制分析表明，LINC01093 可直接结合胰岛素样生长因子 2 mRNA 结合蛋白 1（IGF2BP1），干扰 IGF2BP1 与神经胶质瘤相关癌基因同源物 1（GLI1）mRNA 之间的相互作用。结果是 GLI1 mRNA 的降解，进一步影响 HCC 进展相关的 GLI1 下游分子的表达。富含肝脏的 lncRNA LINC01093 是 HCC 患者有前途的预后指标，新鉴定的 LINC01093-IGF2BP1-GLI1 轴显示出在 HCC 中作为治疗靶点的潜力。
