Identification of circATG9A as a novel biomarker for renal cell carcinoma.

Abstract

The incidence and mortality rates of renal cell carcinoma (RCC) have rapidly increased worldwide. To gain new insights into the regulatory role of circular RNAs (circRNAs) in RCC progression, we conducted RNA sequencing on three pairs of ccRCC and adjacent normal tissues. RT-PCR was utilized to analyze RNA expression. We investigated the effects of circATG9A on RCC cells through various assays including CCK-8, Transwell, wound healing, and colony formation assays. Furthermore, we employed FISH, RNA pull-down, luciferase reporter, and RIP assays to elucidate the mechanism by which circATG9A regulates RCC. Ultimately, we identified 118 differentially expressed circRNAs in RCC, including a novel circRNA, circATG9A, which was found to promote RCC progression both in vitro and in vivo. Moreover, mRNA sequencing, western blotting, and rescue experiments indicated that TRPM3 is the target of circATG9A in RCC progression. Bioinformatic analysis, RNA pull-down, FISH, and RIP assays suggested that circATG9A regulates TRPM3 expression by acting as a sponge for miR-497-5p. Finally, Western blotting revealed that circATG9A promotes the epithelial-mesenchymal transition (EMT) process through the Wnt/β-catenin signaling pathway. Our findings demonstrate that circATG9A is a novel circRNA upregulated in RCC that plays a crucial role in the EMT process through the miR-497-5p/TRPM3/Wnt/β-catenin axis. These results suggest that circATG9A could be a promising target for RCC prognosis and therapy.