Silencing Of hsa_circ_0008450 Represses Hepatocellular Carcinoma Progression Through Regulation Of microRNA-214-3p/EZH2 Axis

Abstract

Tianyu Lin,1,* Yi Dai,1,* Xinli Guo,2 Wenchao Chen,1 Jiangang Zhao,3 Liping Cao,1 Zhengrong Wu1 1Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310000, People’s Republic of China; 2Department of Operating Room, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310000, People’s Republic of China; 3Department of General, Visceral and Tumor Surgery, University Hospital Cologne, Cologne 50934, Germany*These authors contributed equally to this workCorrespondence: Liping Cao; Zhengrong WuDepartment of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, No. 3, Qingchun Road, Hangzhou 310000, People’s Republic of ChinaTel [phone]Fax [phone]Email [email protected]; [email protected]: Circular RNA (circRNA) hsa_circ_0008450 has been shown to be up-regulated in hepatocellular carcinoma (HCC). However, the functional role of hsa_circ_0008450 and its molecular mechanism are still unknown.Patients and methods: We used qRT-PCR and Western blot to examine the expression levels of hsa_circ_0008450, microRNA-214-3p (miR-214-3p), and enhancer of zeste homolog 2 (EZH2) protein. CCK8 assay and wound healing assay were used to detect cell viability and cell migration capability. Cell apoptosis was assessed by flow cytometry. Luciferase reporter assay was used to explore the interaction among hsa_circ_0008450, miR-214-3p, and EZH2.Results: hsa_circ_0008450 was significantly increased in HCC tissues and cells. Furthermore, knockdown of hsa_circ_0008450 in HCC cells inhibited cell proliferation, invasion, and migration. Mechanically, hsa_circ_0008450 promoted the expression of EZH2 protein through sponging miR-214-3p. Knockdown of circ_0008450 suppressed tumorigenesis of HCC cells in vivo.Conclusion: Knockdown of hsa_circ_0008450 inhibits HCC progression by regulating miR-214-3p/EZH2 axis. This study suggests that hsa_circ_0008450 may serve as a novel target for the treatment of HCC.Keywords: circular RNAs, hepatocellular carcinoma, hsa_circ_0008450, miR-214-3p, enhancer of zeste homolog 2

Keywords

• circular RNAs
• hepatocellular carcinoma
• hsa_circ_0008450
• miR-214-3p
• enhancer of zeste homolog 2