CircRNA CircRIMS is Overexpressed in Esophageal Squamous Cell Carcinoma and Downregulate miR-613 Through Methylation to Increase Cell Proliferation

Haijun Wan, Bosi Yuan, Kang Jiang, Juan Wei, Xiaoyue Feng, Bo Sun, Fangyu Wang Department of Gastroenterology, General Hospital of Eastern Theater Command, Nanjing City, Jiangsu Province, 210002, People’s Republic of ChinaCorrespondence: Fangyu WangDepartment of Gastroenterology, General Hospital of Eastern Theater Command, No. 305 East Zhongshan Road, Xuanwu District, Nanjing City, Jiangsu Province, 210002, People’s Republic of ChinaEmail fangyuwangnanjing@163.comPurpose: CircRNA CircRIMS has been characterized as an oncogenic circRNA in gastric cancer, while its role in other cancers is unknown. This study aimed to explore the role of CircRIMS in esophageal squamous cell carcinoma (ESCC).Patients and Methods: Tissues collected from 60 ESCC patients were subjected to extractions of total RNA and RT-qPCRs to analyze the differential expression of CircRIMS and miR-613. The 60 ESCC patients were followed up for 5 years to analyze the prognostic value of CircRIMS for ESCC. The interaction between CircRIMS and miR-613 was showed by luciferase activity assay and fluorescence in situ hybridization. The role of CircRIMS in regulating miR-613 expression and methylation was analyzed by overexpression experiments, RT-qPCRs and Western blot assay. The role of CircRIMS and miR-613 in regulating cell proliferation was analyzed using the BrdU assay. ESCC xenograft model was used to demonstrate the role of CircRIMS and miR-613 in vivo.Results: We found that CircRIMS was overexpressed in ESCC and predicted poor survival. In addition, miR-613 was under expressed in ESCC and inversely correlated with CircRIMS. In ESCC cells, CircRIMS overexpression decreased the expression of miR-613 and increased the methylation of miR-613 gene. Cell proliferation assay showed that CircRIMS overexpression reduced the inhibitory effects of miR-613 overexpression on cell proliferation. Animal experience finally illustrated that CircRNA CircRIMS downregulated miR-613 through methylation to promote tumor growth.Conclusion: Therefore, CircRIMS may downregulate miR-613 through methylation to increase cell proliferation in ESCC.Keywords: esophageal squamous cell carcinoma, CircRIMS, miR-613, proliferation, methylation