A novel circular RNA circ-ZNF652 promotes hepatocellular carcinoma metastasis through inducing snail-mediated epithelial-mesenchymal transition by sponging miR-203/miR-502-5p (Retracted article. See vol. 654, 2023)
A novel circular RNA circ-ZNF652 promotes hepatocellular carcinoma metastasis through inducing snail-mediated epithelial-mesenchymal transition by sponging miR-203/miR-502-5p (Retracted article. See vol. 654, 2023)
复制标题
DOI：
10.1016/j.bbrc.2019.03.214
复制
发表时间：
2019-06-11
影响因子：
3.1
通讯作者：
Yuan, Lu
中科院分区：
文献类型：
--
作者：
Guo, Jianbo;Duan, He;Yuan, Lu
环状RNA（circRNA）是一类特殊的非编码RNA，越来越多地被认为是人类疾病（包括癌症）的关键调节因子。然而，其在肝细胞癌（HCC）转移中的作用仍然很大程度上未知。在此，我们登记了三个基因表达综合（GEO）数据库，筛选并鉴定了一种新的circRNA，circ-ZNF652（hsa_circ_0003258），它在HCC组织和细胞系中显着上调。重要的是，circ-ZNF652高表达的HCC患者更容易发生血管侵犯、肝内转移、远处转移和预后不良。随后的功能实验表明，circ-ZNF652的耗竭通过抑制上皮间质转化（EMT）过程，显着抑制了体外HCC细胞的迁移和侵袭能力以及体内肿瘤转移。从机制上讲，circ-ZNF652可以与miR-203和miR-502-5p物理相互作用，增加其共同靶基因Snail（触发EMT的关键转录因子）的表达，从而促进HCC的转移。反过来，上调的 Snail 能够与 circ-ZNF652 启动子上的 E-box 基序 (CAGGTG) 结合，从而提高 circ-ZNF652 的表达。总的来说，我们的研究结果表明 circ-ZNF652 是 EMT 的新型驱动因素，并揭示了 circ-ZNF652/miR-203/miR-502-5p/Snailfeedback 环在 HCC 转移中的重要调节作用。 (C) 2019 Elsevier Inc. 保留所有权利。
Circular RNA (circRNA), a special class of non-coding RNA, is increasingly being realized as a critical regulator in human diseases, including carcinomas. However, its role in hepatocellular carcinoma (HCC) metastasis remains largely unknown. Herein, we enrolled three Gene Expression Omnibus (GEO) data-bases and screened and identified a novel circRNA, circ-ZNF652 (hsa_circ_0003258), which was significantly upregulated in HCC tissues and cell lines. Importantly, HCC patients with high circ-ZNF652 expression were more prone to vascular invasion, intrahepatic metastasis, distant metastasis, and poor outcome. Subsequent functional experiments showed that depletion of circ-ZNF652 dramatically suppressed the migratory and invasive capabilities of HCC cells in vitro as well as tumor metastasis in vivo by inhibiting the process of epithelial-mesenchymal transition (EMT). Mechanistically, circ-ZNF652 could physically interact with miR-203 and miR-502-5p to increase the expression of their common target gene Snail (a key transcription factor that triggers EMT), thereby promoting the metastasis of HCC. In turn, the upregulated Snail was capable of binding to the E-box motif (CAGGTG) on the promoter of circ-ZNF652 to elevate circ-ZNF652 expression. Collectively, our findings suggest that circ-ZNF652 is a novel driver of EMT and unveil the important regulatory role of circ-ZNF652/miR-203/miR-502-5p/Snailfeedback loop in HCC metastasis. (C) 2019 Elsevier Inc. All rights reserved.