Hepatocellular carcinoma (HCC) is one of the most common malignancies with poor outcomes. The main causes of HCC-related deaths are recurrence and metastasis. Long noncoding RNAs (lncRNAs) are recently identified as critical regulators in cancers. However, the lncRNAs involved in HCC recurrence and metastasis are poorly understood. In this study, via analyzing The Cancer Genome Atlas Liver Hepatocellular Carcinoma dataset, we identified a novel lncRNA LINC01134, which is highly expressed in HCC tissues and correlated with microvascular invasion, macrovascular invasion, recurrence, and poor overall survival of HCC patients. Functional experiments revealed that ectopic expression of LINC01134 promotes HCC cell migration and invasionin vitroand HCC liver metastasis and lung metastasisin vivo. Knockdown of LINC01134 represses HCC cell migration and invasionin vitroand HCC liver metastasis and lung metastasisin vivo. Mechanistically, we found that LINC01134 directly binds the promoter ofAKT1S1and activatesAKT1S1expression. Via activating AKT1S1, LINC01134 further activates NF-kappa B signaling. The expression of LINC01134 is significantly positively correlated with that of AKT1S1 in HCC tissues. In line with LINC01134, AKT1S1 is also highly expressed in HCC tissues and correlated with poor survival of HCC patients. Functional rescue experiments showed that repressing AKT1S1 or NF-kappa B signaling abrogates the roles of LINC01134 in HCC. Taken together, these findings recognized LINC01134 as a novel oncogenic lncRNA, which indicates vascular invasion, recurrence, and poor overall survival of HCC patients. LINC01134 promotes HCC metastasis via activating AKT1S1 expression and subsequently activating NF-kappa B signaling. This study suggested LINC01134 as a potential prognostic biomarker and therapeutic target for HCC.
基金:
National Natural Science Foundation of China [81201554]; Research Fund for Hepatobiliary and Pancreatic Cancer from Hubei Chen Xiaoping Foundation for Scientific and Technological Development [CXPJJH11900001-2019346]; Start Up Fund for Returnees from Tongji Hospital [2019HGRY002]
第一作者单位:[1]Huazhong Univ Sci & Technol, Tongji Med Coll, Dept Gen Surg, Clin Res Ctr Geriatr Dis Hubei Prov, Wuhan, Peoples R China
通讯作者:
通讯机构:[4]Huazhong Univ Sci & Technol,Tongji Med Coll,Tongji Hosp,Hepat Surg Ctr,Key Lab Organ Transplantat,Minist,Wuhan,Peoples R China[5]Huazhong Univ Sci & Technol,Tongji Med Coll,Tongji Hosp,Minist Publ Hlth,Wuhan,Peoples R China
推荐引用方式(GB/T 7714):
Wang Chao,Chen Yan,Chen Kunlun,et al.Long Noncoding RNA LINC01134 Promotes Hepatocellular Carcinoma Metastasis via Activating AKT1S1 and NF-κB Signaling[J].FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY.2020,8:doi:10.3389/fcell.2020.00429.
APA:
Wang, Chao,Chen, Yan,Chen, Kunlun&Zhang, Lei.(2020).Long Noncoding RNA LINC01134 Promotes Hepatocellular Carcinoma Metastasis via Activating AKT1S1 and NF-κB Signaling.FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY,8,
MLA:
Wang, Chao,et al."Long Noncoding RNA LINC01134 Promotes Hepatocellular Carcinoma Metastasis via Activating AKT1S1 and NF-κB Signaling".FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY 8.(2020)