OncoTargets and Therapy (May 2020)
Circular RNA Gprc5a Promotes HCC Progression by Activating YAP1/TEAD1 Signalling Pathway by Sponging miR-1283
Abstract
Ye Lin,1,* Guanqun Huang,2,* Haosheng Jin,1,* Zhixiang Jian1 1Department of General Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, People’s Republic of China; 2Department of General Surgery, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou 510700, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhixiang JianDepartment of General Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan Er Road, Guangzhou 510080, People’s Republic of ChinaEmail [email protected]: Circular RNA (circRNA) plays a critical role in tumorigenesis and tumor progression. Many studies indicate that circRNA Gprc5a is significantly upregulated and functions as an oncogene in a variety of cancers. However, the molecular mechanism of circGprc5a in liver cancer remains unclear.Methods: qRT-PCR was used to measure the expression levels of circGprc5a, miR-1283, YAP1 and TEAD1 mRNA in hepatocellular carcinoma (HCC) tissues or cells. YAP1 and TEAD1 protein levels were detected by Western blot. CCK-8 assay, cell colony formation, BrdU incorporation and Annexin V-FITC/PI assays were performed to analyze the effects of circGprc5a and miR-1283 on cell proliferation and apoptosis. The relationship between circGprc5a, miR-1283, YAP1 and TEAD1 was analyzed using bioinformatic analysis and luciferase. The tumor changes in mice were detected by in vivo experiments.Results: CircGprc5a was highly expressed in liver cancer, and closely related poor survival of patients with liver cancer. Knockout of circGprc5a inhibited proliferation of HCC and induced apoptosis. CircGprc5a activated the YAP1/TEAD1 signaling pathway by acting as a sponge for miR-1283. Furthermore, overexpression of miR-1283 abolished the promotion of circGprc5a on HCC cells. Therefore, miR-1283 expression correlated negatively with circGprc5a expression yet positively with the expression of YAP1/TEAD1 in liver cancer.Conclusion: CircGprc5a promoted the development of HCC by inhibiting the expression of miR-1283 and activating the YAP1/TEAD1 signaling pathway.Keywords: circGprc5a, miR-1283, YAP1/TEAD1, HCC, proliferation
