Second Clinical Medical College, Zhejiang Chinese Medical University, 548 Binwen Road, Hangzhou 310053, China.
Department of Ultrasound, Renmin Hospital of Wuhan University, Jiefang Road 238, Wuhan 430060, China.
Cell Signal. 2020 Aug;72:109621. doi: 10.1016/j.cellsig.2020.109621. Epub 2020 Mar 30.
Circular RNAs (circRNAs) have been reported to regulate the gene expression through sponging corresponding microRNAs in multiple malignant tumors, including hepatocellular carcinoma (HCC). Up to now, the effects of circ_0001178 in HCC are barely known. In our current work, we tested circ_0001178 expression in HCC tissues and HCC cells and found it was greatly elevated. Then, we evaluated the function of circ_0001178 on HCC cell proliferation. We found HepG2 and Huh-7 cell proliferation was repressed after circ_0001178 shRNA was infected into the cells. Moreover, flow cytometry evidenced that HepG2 and Huh-7 cell apoptosis was markedly triggered and cell cycle was arrested. Meanwhile, it was shown that HCC cell migration and invasion capacity were markedly inhibited by loss of circ_0001178. Knockdown of circ_0001178 restrained HCC tumor growth in vivo. Then, miR-382 was predicted and confirmed as the target of circ_0001178. Circ_0001178 was demonstrated to modulate miR-382 expression negatively. The effect of circ_0001178 on HCC tumor was rescued by miR-382 overexpression. Furthermore, vascular epithelial growth factor A (VEGFA) is identified in various cancers. Currently, VEGFA was proved to be the downstream target of miR-382. To conclude, this research revealed that circ_0001178 induced HCC progression via modulating miR-382 and VEGFA axis.
环状 RNA（circRNAs）已被报道通过海绵吸附相应的 microRNAs 在多种恶性肿瘤中调节基因表达，包括肝细胞癌（HCC）。到目前为止，circ_0001178 在 HCC 中的作用知之甚少。在我们目前的工作中，我们检测了 HCC 组织和 HCC 细胞中的 circ_0001178 表达，发现其表达显著上调。然后，我们评估了 circ_0001178 对 HCC 细胞增殖的影响。我们发现，感染 circ_0001178 shRNA 后 HepG2 和 Huh-7 细胞的增殖受到抑制。此外，流式细胞术证实 HepG2 和 Huh-7 细胞的凋亡明显被触发，细胞周期被阻滞。同时，circ_0001178 的缺失明显抑制了 HCC 细胞的迁移和侵袭能力。circ_0001178 的敲低抑制了 HCC 肿瘤在体内的生长。然后，预测并证实 miR-382 是 circ_0001178 的靶基因。circ_0001178 被证明能负调控 miR-382 的表达。miR-382 过表达挽救了 circ_0001178 对 HCC 肿瘤的影响。此外，血管内皮生长因子 A（VEGFA）在各种癌症中被鉴定出来。目前，已经证明 VEGFA 是 miR-382 的下游靶基因。总之，这项研究揭示了 circ_0001178 通过调节 miR-382 和 VEGFA 轴诱导 HCC 进展。
