The long noncoding RNA NORAD enhances the TGF- pathway to promote hepatocellular carcinoma progression by targeting miR-202-5p
The long noncoding RNA NORAD enhances the TGF- pathway to promote hepatocellular carcinoma progression by targeting miR-202-5p
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长非编码RNA NORAD通过靶向miR-202-5p增强TGF-通路促进肝细胞癌进展
DOI：
10.1002/jcp.27869
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发表时间：
2019-07-01
影响因子：
5.6
通讯作者：
Fan, Jia
中科院分区：
文献类型：
--
作者：
Yang, Xuan;Cai, Jia-Bin;Fan, Jia
肝细胞癌是最致命的癌症之一，具有侵袭和转移的共同特征。最近的证据表明，长的非编码RNA NORAD是一个潜在的癌基因，在几种癌症中显著上调。然而，NORAD在肝细胞癌中的一般生物学作用和临床价值仍不清楚。在这里，通过定量实时聚合酶链式反应(QPCR)检测了29对肿瘤和癌旁组织中NORAD的表达。通过体内和体外NORAD的过表达和基因敲除来研究NORAD对肝癌细胞恶性潜能的影响。通过生物信息学分析和荧光素酶分析，获得并鉴定了竞争内源RNA(CeRNAs)的机制。此外，通过定量聚合酶链式反应进一步检测了NORAD水平对转化生长因子(TGF-α)途径的影响。我们发现，与癌旁组织相比，肝癌组织中NORAD的表达水平较高，并且NORAD上调与肝癌患者的总生存期缩短有关。此外，NORAD的过表达被证明促进了肝癌细胞的迁移和侵袭。从机制上讲，NORAD可能作为Cerna调节miR-202-5p，而miR-202-5p通过转化生长因子途径作为抑制肿瘤的microRNA。我们认为NORAD在肝癌中具有促进肿瘤的作用，并描述了一种新的机制，即NORAD作为人的CENA(Hsa)-miR-202-5p调节转化生长因子途径。
Hepatocellular carcinoma (HCC) is one of the most fatal cancers with common features of invasion and metastasis. Recent evidence indicate that the long noncoding RNA NORAD is a potential oncogene and is significantly upregulated in several cancers. However, the general biological role and clinical value of NORAD in HCC remains unknown. Here, NORAD expression was measured in 29 paired tumor and paratumor tissues via quantitative real-time polymerase chain reaction (qPCR). The effects of NORAD on HCC cell malignant potential were investigated via NORAD overexpression and knockdown both in vitro and in vivo. The mechanism of competitive endogenous RNAs (ceRNAs) was acquired and identified by bioinformatics analyses and luciferase assays. Moreover, the impact of NORAD level on the transforming growth factor (TGF-) pathway was further determined by qPCR. We found that HCC tissues had a high level of NORAD compared with the paratumor tissues, and NORAD upregulation was associated with the shorter overall survival of patients with HCC. Furthermore, NORAD overexpression was demonstrated to promote HCC cell migration and invasion. Mechanically, NORAD might function as a ceRNA to regulate miR-202-5p, which served as a tumor-suppressing microRNA via the TGF- pathway. We address that NORAD has a tumor-promoting effect in HCC and describes a novel mechanism whereby NORAD regulates the TGF- pathway as a ceRNA of Homo sapiens (hsa)-miR-202-5p.