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环状 RNA circ_0067934 通过调控 miR-1324/FZD5/Wnt/β-连环蛋白轴促进肝癌的生长和转移。

CircRNA circ_0067934 promotes tumor growth and metastasis in hepatocellular carcinoma through regulation of miR-1324/FZD5/Wnt/β-catenin axis.

机构信息

Department of Gastroenterology, Shenzhen Longhua District Central Hospital, Shenzhen 518029, China.

Department of General Surgical, The Second People's Hospital of Shenzhen, Shenzhen 518029, China.

出版信息

Biochem Biophys Res Commun. 2018 Mar 4;497(2):626-632. doi: 10.1016/j.bbrc.2018.02.119. Epub 2018 Feb 16.

Abstract

Recently, increasing evidences demonstrate that circular RNAs (circRNAs) exert very important functions in the progression of human cancers. However, the functions and molecular mechanism of circ_0067934 in hepatocellular carcinoma (HCC) are largely unknown. In the present study, we found that the expression of circ_0067934 was significantly upregulated in HCC tissues and cell lines compared to adjacent normal tissues. Furthermore, we showed that circ_0067934 knockdown remarkably suppressed the proliferation, migration and invasion of Hep3B and HuH7 cells while inducing their apoptosis. In terms of mechanism, we found that circ_0067934 directly suppressed miR-1324, which targeted the 3'-UTR of FZD5 mRNA and subsequently downregulated the Wnt/β-catenin signaling pathway in HCC. Through rescue experiments, we demonstrated that circ_0067934 enhanced the proliferation, migration and invasion of HCC cells by the inhibition of miR-1324 and concomitant activation of FZD5/Wnt/β-catenin signaling pathway. In summary, the circ_0067934/miR-1324/FZD5/β-catenin signaling axis might serve as a promising therapeutic target for HCC intervention.

摘要

最近,越来越多的证据表明环状 RNA(circRNAs)在人类癌症的进展中发挥着非常重要的作用。然而,circ_0067934 在肝细胞癌(HCC)中的功能和分子机制在很大程度上是未知的。在本研究中,我们发现与相邻正常组织相比,circ_0067934 在 HCC 组织和细胞系中的表达明显上调。此外,我们表明 circ_0067934 的敲低显著抑制了 Hep3B 和 HuH7 细胞的增殖、迁移和侵袭,同时诱导了它们的凋亡。就机制而言,我们发现 circ_0067934 直接抑制了 miR-1324,miR-1324 靶向 FZD5 mRNA 的 3'UTR,随后下调了 HCC 中的 Wnt/β-catenin 信号通路。通过挽救实验,我们证明 circ_0067934 通过抑制 miR-1324 和同时激活 FZD5/Wnt/β-catenin 信号通路来增强 HCC 细胞的增殖、迁移和侵袭。总之,circ_0067934/miR-1324/FZD5/β-catenin 信号轴可能成为 HCC 干预的有前途的治疗靶点。

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