Liu Xialei, Yang Lewei, Jiang Dong, Lu Wuzhu, Zhang Yongyu
Department of Hepatobiliary Surgery, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai City, Guangdong Province 519000 China.
Department of Radiotherapy for Abdominal Neoplasms, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai City, Guangdong Province 519000 China.
Cancer Cell Int. 2020 Jul 8;20:295. doi: 10.1186/s12935-020-01346-0. eCollection 2020.
Hepatocellular carcinoma (HCC) is a common malignant tumor in China. Advanced treatment like transcatheter hepatic arterial chemoembolization (TACE) has prolonged the lives of many HCC patients. However, the prognosis of most HCC patients remains unsatisfactory. Recently, circular RNAs (circRNAs) have been gradually unveiled to exert considerable functions in cancer. Promising circRNAs in HCC remains to be further elucidated.
Gene expression was assessed by qRT-PCR and western blot. The function of circ-DENND4C in HCC was estimated by both in vitro and in vivo experiments. The location of circ-DENND4C in HCC cells was determined by subcellular fractionation and FISH assays. The association among molecules were analyzed through RNA pull down, RIP and luciferase reporter assays.
circ-DENND4C (DENN domain containing 4C), an oncogene identified in breast cancer, was overexpressed in HCC cells. Also, circ-DENND4C exerted pro-tumor functions in HCC through activating Wnt/β-catenin pathway. Importantly, circ-DENND4C could augment transcription factor 4 (TCF4) expression to activate Wnt/β-catenin signaling via sequestering miR-195-5p. Moreover, following rescue assays disclosed that circ-DENND4C mediated malignant phenotypes in HCC cells via up-regulating TCF4 through sponging miR-195-5p.
circ-DENND4C boosted TCF4 expression to modulate malignant behaviors of HCC cells via activating Wnt/β-catenin pathway, which might offer a promising target for HCC treatment.
肝细胞癌（HCC）是中国常见的恶性肿瘤。经导管肝动脉化疗栓塞术（TACE）等先进治疗方法延长了许多HCC患者的生命。然而，大多数HCC患者的预后仍不尽人意。近年来，环状RNA（circRNA）在癌症中的重要功能逐渐被揭示。HCC中具有潜力的circRNA仍有待进一步阐明。
通过qRT-PCR和蛋白质免疫印迹法评估基因表达。通过体外和体内实验评估circ-DENND4C在HCC中的功能。通过亚细胞分级分离和荧光原位杂交实验确定circ-DENND4C在HCC细胞中的定位。通过RNA下拉、RNA免疫沉淀和荧光素酶报告基因实验分析分子间的相互作用。
circ-DENND4C（含DENN结构域蛋白4C）是在乳腺癌中鉴定出的一种致癌基因，在HCC细胞中过表达。此外，circ-DENND4C通过激活Wnt/β-连环蛋白信号通路在HCC中发挥促肿瘤作用。重要的是，circ-DENND4C可以通过隔离miR-195-5p来增加转录因子4（TCF4）的表达，从而激活Wnt/β-连环蛋白信号通路。此外，挽救实验表明，circ-DENND4C通过海绵吸附miR-195-5p上调TCF4，从而介导HCC细胞的恶性表型。
circ-DENND4C通过激活Wnt/β-连环蛋白信号通路促进TCF4表达，从而调节HCC细胞的恶性行为，这可能为HCC治疗提供一个有前景的靶点。
