A novel, liver-specific long noncoding RNA LINC01093 suppresses HCC progression by interaction with IGF2BP1 to facilitate decay of GLI1 mRNA

被引:102
作者
He, Jia [1 ]
Zuo, Qiaozhu [1 ]
Hu, Bo [2 ,3 ]
Jin, Haojie [1 ]
Wang, Cun [1 ]
Cheng, Zhuoan [4 ]
Deng, Xuan [5 ]
Yang, Chen [5 ]
Ruan, Haoyu [5 ]
Yu, Chengtao [4 ]
Zhao, Fangyu [1 ]
Yao, Ming [1 ]
Fang, Jingyuan [1 ]
Gu, Jianren [1 ]
Zhou, Jian [2 ,3 ]
Fan, Jia [2 ,3 ]
Qin, Wenxin [1 ]
Yang, Xin-Rong [2 ,3 ]
Wang, Hui [1 ]
机构
[1] Shanghai Jiao Tong Univ, Sch Med, State Key Lab Oncogenes & Related Genes, Shanghai Canc Inst,Renji Hosp, 25 Ln2200 Xie Tu Rd, Shanghai 200032, Peoples R China
[2] Fudan Univ, Liver Canc Inst, Zhongshan Hosp, Dept Liver Surg, Shanghai 200032, Peoples R China
[3] Fudan Univ, Key Lab Carcinogenesis & Canc Invas, Minist Educ, Shanghai 200032, Peoples R China
[4] Shanghai Jiao Tong Univ, Sch Biomed Engn, Shanghai 200030, Peoples R China
[5] Fudan Univ, Shanghai Med Coll, Shanghai 200032, Peoples R China
基金
中国国家自然科学基金;
关键词
lncRNA; Proliferation; Metastasis; mRNA stability; Post-transcriptional regulation; HEDGEHOG SIGNALING PATHWAY; HEPATOCELLULAR-CARCINOMA; SONIC HEDGEHOG; CELL-MIGRATION; CANCER-CELLS; PROMOTES; RECOGNITION; METASTASIS; ACTIVATION; INVASION;
D O I
10.1016/j.canlet.2019.02.033
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:98 / 109
页数:12
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