CircHGS enhances the progression of bladder cancer by regulating the miR-513a-5p/VEGFC axis and activating the AKT/mTOR signaling pathway

Abstract

BackgroundBladder cancer (BCa) is a malignant tumor that occurs in the bladder mucosa with high mortality. Circular RNAs (circRNAs), newly discovered noncoding RNAs, are associated with the occurrence and development of BCa. However, the effects of circRNAs in BCa have not been fully elucidated. Through the GEO (Gene Expression Omnibus) database, an abnormally expressed circular RNA, circHGS (hsa_circ_0004721), was rst identi ed in BCa. In this study, we clari ed the roles and potential mechanism of circHGS in BCa progression. MethodsThe level of circHGS in tissue and cell was assessed by qRT-PCR. The proliferation, migration and invasion of BCa cells were detected by CCK8, colony formation assay, wound-healing assay, and Transwell assays, respectively. The interaction between circHGS/VEGFC and miR-513a-5p was detected by dual luciferase and qRT-PCR. VEGFC protein level was detected by western blotting. Nude mouse xenograft model was used to clarify the role of circHGS in tumor growth in vivo. ResultsCircHGS, originating from the HGS gene, is upregulated in BCa tissues compared to normal tissues.Functionally, silencing of circHGS apparently suppressed BCa cell proliferation, migration and invasion, but circHGS overexpression showed the opposite result. In vivo experiments also suggested that knockdown of circHGS suppressed tumor growth. Mechanistically, circHGS functions as a sponge of miR-513a-5p to elevate VEGFC expression and activate the AKT/mTOR signaling pathway, ultimately promoting BCa progression. ConclusionOur ndings indicated that circHGS promotes BCa progression via the miR-513a-5p/VEGFC/AKT/mTOR pathway and can be a promising therapeutic target of BCa.