Cancer Management and Research (May 2022)
CirRNA F-circEA-2a Suppresses the Role of miR-3613-3p in Colorectal Cancer by Direct Sponging and Predicts Poor Survival
Abstract
Fu Xiang, Xuedong Xu Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian City, Liaoning Province, People’s Republic of ChinaCorrespondence: Xuedong Xu, Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, No. 5 Longbin Road, Dalian City, Liaoning Province, 116000, People’s Republic of China, Tel +86-83635963-7098, Email [email protected]: CirRNA F-circEA-2a and miR-3613-3p are two recently identified novel cancer-related RNAs. To date, their participation in colorectal cancer (CRC) is unknown. This research was therefore conducted to analyze their participation in CRC.Patients and Methods: Plasma and paired CRC and non-tumor tissues from CRC patients (n=64) and plasma samples from healthy controls (HCs, n=64) were collected. F-circEA-2a and miR-3613-3p levels in these samples were analyzed using RT-qPCR. The 64 CRC patients were followed up for five years to analyze the prognostic value of plasma F-circEA-2a for CRC. The direct interaction between wild type F-circEA-2a (F-circEA-2a-wt) or mutant F-circEA-2a (F-circEA-2a-mut) and miR-3613-3p was analyzed through RNA-RNA pulldown assay. The role of F-circEA-2a and miR-3613-3p in regulating each other’s expression was analyzed through overexpression assay. Their roles in cell proliferation were analyzed using BrdU assay. The role of F-circEA-2a in regulating EZH2 expression was analyzed by RT-qPCR and Western blot.Results: CircEA-2a was overexpressed in CRC, while miR-3613-3p was under-expressed in CRC. Most patients who died during the follow-up had high F-circEA-2a levels. F-circEA-2a-wt, but not F-circEA-2a-mut, directly interacted with miR-3613-3p. F-circEA-2a and miR-3613-3p showed no role in regulating each other’s expression. F-circEA-2a reduced the inhibitory effects of miR-3613-3p on cell proliferation. F-circEA-2a upregulated EZH2 at both mRNA and protein levels.Conclusion: F-circEA-2a may suppress the role of miR-3613-3p in CRC by direct sponging and predicts poor survival.Keywords: F-circEA-2a, miR-3613-3p, colorectal cancer, prognosis