circ_0003418 Inhibits Tumorigenesis And Cisplatin Chemoresistance Through Wnt/β-Catenin Pathway In Hepatocellular Carcinoma

• Main Authors: Chen H, Liu S, Li M, Huang P, Li X
• Format: Article
• Language: English
• Published: Dove Medical Press 2019-11-01
• Series: OncoTargets and Therapy
• Subjects: circular rna; circ-0003418; hepatocellular carcinoma; cisplatin resistance; wnt/β‐catenin
• Online Access: https://www.dovepress.com/circ0003418-inhibits-tumorigenesis-and-cisplatin-chemoresistance-throu-peer-reviewed-article-OTT
• ISSN: 1178-6930

Hang Chen,1 Shan Liu,1 Molin Li,2 Ping Huang,2 Xiaoping Li1 1Department of Oncology and Hematology, The People’s Hospital of Tongliang District, Chongqing 402560, People’s Republic of China; 2Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing Medical University, Chongqing 400000, People’s Republic of ChinaCorrespondence: Xiaoping LiDepartment of Oncology and Hematology, The People’s Hospital of Tongliang District, 528# Zhongxing East Road, Dongcheng Street, Tongliang District, Chongqing 402560, People’s Republic of ChinaTel [phone]Email [e-mail]   Ping HuangNational Key Clinical Department, Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing Medical University, Chongqing 400000, People’s Republic of ChinaTel [phone]Email [e-mail]: Accumulating evidences indicate that circRNAs play important roles in the progression and chemoresistance of human cancers. The present study is designated for researching the roles of circ_0003418 in hepatocellular carcinoma (HCC).Methods: We detected the expression profile of circ_0003418 in human HCC tissues and cell lines by quantitative real-time-PCR assays. CCK-8 assay, transwell migration assay, transwell invasion assay and drug-sensitivity analysis were carried out to estimate the effects of circ_0003418 on HCC cells’ proliferation, migration, invasion and resistance to cisplatin, respectively. Mouse xenograft model was conducted to monitor the role of circ_0003418 in cisplatin resistance in vivo. Western blotting was performed to explore the changes of the Wnt/β-catenin pathway after knockdown of circ_0003418. The rescue experiment was carried out to explore circ_0003418-activated biological functions through Wnt/β-catenin pathway.Results: The expression level of circ_0003418 was downregulated in HCC tissues and cell lines, and the level correlated with tumor size, TNM stage and HBsAg level in HCC patients. circ_0003418 knockdown promoted HCC cells’ proliferation, migration, and invasion. Additionally, suppression of circ_0003418 enhanced cisplatin resistance of HCC cells in vivo and vitro. Knockdown of circ_0003418 activated the Wnt/β-catenin signalling pathway in HCC cells. The effect of circ-0003418 on sensitivity of HCC cells to cisplatin was reversed after inhibition of Wnt/β-catenin pathway.Conclusion: circ-0003418 exerts an antitumorigenic role in HCC and advances the sensitivity of HCC cells to cisplatin by restraining the Wnt/β-catenin pathway. Thus, circ-0003418 may represent a novel biomarker and provide us a new strategy for the treatment of HCC.Keywords: circRNA, circ-0003418, hepatocellular carcinoma, cisplatin resistance, Wnt/β-catenin