Circular RNA profiling identifies circADAMTS13 as a miR-484 sponge which suppresses cell proliferation in hepatocellular carcinoma
Circular RNA profiling identifies circADAMTS13 as a miR-484 sponge which suppresses cell proliferation in hepatocellular carcinoma
复制标题
环状 RNA 分析将 circADAMTS13 鉴定为 miR-484 海绵，可抑制肝细胞癌中的细胞增殖
DOI：
10.1002/1878-0261.12424
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发表时间：
2019-02-01
影响因子：
6.6
通讯作者：
Liu, Jingfeng
中科院分区：
文献类型：
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作者：
Qiu, Liman;Huang, Yanbing;Liu, Jingfeng
环状RNA（circRNA）可以通过其microRNA反应元件参与各种生物学过程，包括肿瘤发生。肝细胞癌（HCC）进展过程中circRNA谱的变化及其临床意义仍不清楚。在此，我们对收集自10例HCC患者的肿瘤和匹配的瘤周组织中的circRNA谱进行了广泛的分析，以确定与HCC进展相关的circRNA。与匹配的癌旁组织相比，在HCC肿瘤组织中总共鉴定出42种失调的circRNA（38种下调和4种上调），揭示了HCC中circRNA谱的异质性。来自ADAMTS 13基因外显子13-14的CircADAMTS 13在HCC肿瘤组织中显著下调。此外，临床病理分析显示，circADAMTS 13的上调与肿瘤大小呈负相关，但与预后呈正相关。此外，过表达circADAMTS 13可显著抑制肝癌细胞的体外增殖。生物信息学分析和荧光素酶报告基因分析进一步揭示了circADAMTS 13与microRNA（miR）-484直接相互作用。拯救实验表明，miR-484模拟物可以逆转circADAMTS 13在HCC中的肿瘤抑制作用。因此，我们的研究结果表明，circADAMTS 13可以通过海绵状miR-484的功能途径在HCC进展期间作为肿瘤抑制因子。
Circular RNA (circRNA) can participate in various biological processes, including tumorigenesis, through their microRNA response elements. Alterations in circRNA profiles during hepatocellular carcinoma (HCC) progression and their clinical significance remain unclear. Here, we present extensive analysis of circRNA profiles in tumor and matched peritumor tissues collected from 10 HCC patients, conducted to identify circRNA related to HCC progression. A total of 42 dysregulated circRNA (38 down-regulated and 4 up-regulated) were identified in HCC tumor tissues compared with matched peritumor tissues, revealing the heterogeneity of circRNA profiles in HCC. CircADAMTS13, derived from Exon 13-14 of the ADAMTS13 gene, was significantly downregulated in HCC tumor tissues. Furthermore, clinicopathological analysis revealed that up-regulation of circADAMTS13 was negatively associated with tumor size but positively associated with prognosis. In addition, overexpression of circADAMTS13 could markedly inhibit HCC cell proliferation in vitro. Bioinformatic analysis and luciferase reporter assays further revealed that circADAMTS13 directly interacts with microRNA (miR)-484. Rescue experiments showed that miR-484 mimics can reverse the tumor-suppressing roles of circADAMTS13 in HCC. Therefore, our results demonstrated that circADAMTS13 can serve as a tumor suppressor during HCC progression via the functional pathway of sponging miR-484.