Super-Enhancer-Associated Long Noncoding RNA HCCL5 Is Activated by ZEB1 and Promotes the Malignancy of Hepatocellular Carcinoma
Super-Enhancer-Associated Long Noncoding RNA HCCL5 Is Activated by ZEB1 and Promotes the Malignancy of Hepatocellular Carcinoma
复制标题
超级增强子相关长非编码RNA HCCL5被ZEB1激活促进肝细胞癌恶性
DOI：
10.1158/0008-5472.can-18-0367
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发表时间：
2019-02-01
期刊：
影响因子：
11.2
通讯作者：
Lin, De-Chen
中科院分区：
文献类型：
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作者：
Peng, Li;Jiang, Binyuan;Lin, De-Chen
肝细胞癌（HCC）是全球肿瘤相关死亡的最主要原因之一。在这项研究中，我们确定和表征HCCL 5，一种新的细胞质长非编码RNA（lncRNA），作为一个重要的癌基因在肝癌。HCCL 5在体外和体内均能促进肝癌细胞的生长、G1-S转化、侵袭和转移，并能抑制肝癌细胞的凋亡。此外，HCCL 5在TGF-β 1诱导的经典上皮-间充质转化（EMT）模型中上调，这种lncRNA反过来通过上调转录因子Snail、Slug、ZEB 1和Twist 1的表达来加速EMT表型。HCCL 5由ZEB 1通过超级增强子转录驱动，并且在人HCC组织中显著且频繁地过表达，与HCC患者的总体生存率较差相关。总之，这项研究将HCCL 5表征为促进HCC细胞活力，迁移和EMT的超级增强子驱动的lncRNA。我们的数据还表明，HCCL 5可能作为一个新的预后生物标志物和治疗靶点在hchc.Significance：这些研究结果确定lncRNA HCCL 5作为一个超级增强子驱动的致癌因子，促进肝细胞癌的恶性。
Hepatocellular carcinoma (HCC) is one of the most dominant causes of neoplasm-related deaths worldwide. In this study, we identify and characterize HCCL5, a novel cytoplasmic long noncoding RNA (lncRNA), as a crucial oncogene in HCC. HCCL5 promoted cell growth, G(1)-S transition, invasion, and metastasis while inhibiting apoptosis of HCC cells both in vitro and in vivo. Moreover, HCCL5 was upregulated in TGF-beta 1-induced classical epithelial-to-mesenchymal transition (EMT) models, and this lncRNA in turn accelerated the EMT phenotype by upregulating the expression of transcription factors Snail, Slug, ZEB1, and Twist1. HCCL5 was transcriptionally driven by ZEB1 via a super-enhancer and was significantly and frequently overexpressed in human HCC tissues, correlating with worse overall survival of patients with HCC. Together, this study characterizes HCCL5 as a super-enhancer-driven lncRNA promoting HCC cell viability, migration, and EMT. Our data also suggest that HCCL5 may serve as a novel prognostic biomarker and therapeutic target in HCC.Significance: These findings identify the lncRNA HCCL5 as a super-enhancer-driven oncogenic factor that promotes the malignancy of hepatocellular carcinoma.