Hsa_circ_0002198 mediated by EIF4A3 promotes the proliferation and cell cycle progression of keloid fibroblasts

Abstract

AbstractBackground and Objectives Emerging evidence suggests that Circular RNAs (circRNAs) play important biological role in keloid diseases, but the underlying mechanism remains unclear. In the present study, we investigated the biological effects and molecular mechanisms of hsa_circ_0002198 in keloid formation. Methods Real-time quantitative PCR (qRT-PCR) was used to detect circ_0002198 expression in keloid tissues, normal skin tissues, keloid fibroblasts (KFs) and normal skin fibroblasts(NFs). To study the function of circ_0002198 in kelkelite, we used cell transfection technology to knock down circ_0002198. Cell counting kit-8༈CCK-8༉, 5-Ethynyl-2’-deoxyuridine༈EdU༉, Transwell, wound healing assay, flow cytometry and other experiments were used to study the potential mechanism of circ_0002198 expression. The RNA-binding protein Eukaryotic translation initiation factor 4A,isoform 3༈EIF4A3༉bound to circ_0002198 was identified and confirmed using bioinformatics database prediction and RNA immunoprecipitation ༈RIP༉assay. The expression of EIF4A3 was detected and interfered to verify the correlation between EIF4A3 and circ_0002198. Results The expression levels of circ_0002198 and EIF4A3 in keloid and KFs were significantly higher than in normal skin and NFs. Decreasing circ_0002198 expression in KFs significantly inhibits the proliferation, migration, and invasion of KFs, block the cell cycle process and expression of related proteins, and promote apoptosis in KFs. EIF4A3 can bind to the flanks of circ_0002198 and mediate the occurrence of circ_0002198, jointly regulating KF function. Conclusion Circ_0002198 regulates the proliferation, migration, invasion, and apoptosis of KFs and blocks their cell cycle process. EIF4A3 is mediated by targeted binding to circ_0002198, thus affecting the biological functions of KFs.