CirRNA F-circEA-2a Suppresses the Role of miR-3613-3p in Colorectal Cancer by Direct Sponging and Predicts Poor Survival

PURPOSE: 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.