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