There is emerging evidence that circular RNAs (circRNAs) act as important regulators in various cancers. It is less clear, however, what role circRNA plays in the tumorigenesis and metastasis of clear cell renal cell carcinoma (ccRCC). In this study, using bioinformatics analysis and a series of experimental analysis, we characterized a novel circRNA, hsa_circ_0085576 was up-regulated in ccRCC tissues and cell lines. High hsa_circ_0085576 expression was significantly correlated with tumor size, clinical stage, and metastasis status and poorer survival. Knockdown of hsa_circ_0085576 notably inhibited cell proliferation, migration, invasion, whereas enhanced cell apoptosis of ccRCC cells, in vitro. In contrast, overexpression of hsa_circ_0085576 had the opposite effects. Moreover, hsa_circ_0085576 silencing significantly suppressed tumor growth and metastasis, whereas overexpression of hsa_circ_0085576 had the opposite effects, in vivo, Our results further showed that hsa_circ_0085576 acted as a competitive endogenous RNAs to interact with microRNA-498, to attenuate its repressive effect on target gene Yes-associated protein 1 (YAP1). Finally, functional studies revealed that inhibition of hsa_circ_0085576 suppressed cell growth and metastasis by regulating miR-498/YAP1 signaling, in ccRCC cells. Based on these findings, hsa_circ_0085576 may represent a valuable prognostic biomarker and a potential therapeutic target to curb the tumorigenesis and metastasis of ccRCC.
Keywords: clear cell renal cell carcinoma; has-hsa_circ_0085576; microRNA-498; yes-associated protein 1.