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首页> 外文期刊>Biochemical and Biophysical Research Communications >A novel circular RNA circ-ZNF652 promotes hepatocellular carcinoma metastasis through inducing snail-mediated epithelial-mesenchymal transition by sponging miR-203/miR-502-5p
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A novel circular RNA circ-ZNF652 promotes hepatocellular carcinoma metastasis through inducing snail-mediated epithelial-mesenchymal transition by sponging miR-203/miR-502-5p

机译：新颖的圆形RNA循环ZnF652通过冲水MiR-203 / miR-502-5P诱导蜗牛介导的上皮 - 间充质转化来促进肝细胞癌转移促进肝细胞癌转移

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摘要

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) databases 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/Snail feedback loop in HCC metastasis.
机译：圆形RNA（CircrNA）是一种特殊的非编码RNA，越来越多地被实现为人类疾病中的临界调节因子，包括癌。然而，它在肝细胞癌（HCC）转移中的作用仍然很大程度上是未知的。在此，我们注册了三种基因表达综合征（Geo）数据库并筛选并鉴定了一种新的CircrNA，ZnF652（HSA_CIRC_0003258），其在HCC组织和细胞系中显着上调。重要的是，HCC患者具有高ZnF652表达的患者更容易发生血管侵袭，肝内转移，远处转移和差的结果。随后的功能实验表明，通过抑制上皮 - 间充质转换（EMT）的过程，耗尽循环ZNF652在体外，在体外，体外肿瘤的迁移和侵袭能力以及体内的肿瘤转移。机械上，循环ZnF652可以与miR-203和miR-502-5p进行物理相互作用以增加其常见的靶基因蜗牛的表达（触发EMT的关键转录因子），从而促进HCC转移。反过来，上调的蜗牛能够与循环ZnF652的启动子上的E-Box基序（CAGGTG）结合，以提高ZnF652表达。统称，我们的研究结果表明，Circ-ZNF652是EMT的新推动力，并揭示了HCC转移中的Circ-ZNF652 / MIR-203 / MIR-502-5P /蜗牛反馈环路的重要监管作用。

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