Circ_RPL23A acts as a miR-1233 sponge to suppress the progression of clear cell renal cell carcinoma by promoting ACAT2

Abstract

Background Clear cell renal cell carcinoma (CCRCC) is a prevalent urological carcinoma with high metastatic risk. Circular RNAs (circRNAs) have been identified as effective diagnostic and therapeutic biomarkers for CCRCC. This research aims to disclose the involvement of circRNA ribosomal protein L23a (circ_RPL23A) in CCRCC, and how it regulates carcinogenesis. Methods We performed quantitative real-time polymerase chain reaction (qRT-PCR) to examine circ_RPL23A, microRNA-1233 (miR-1233) and acetyl-coenzyme A acetyltransferase 2 (ACAT2). Cellular behavior detection included cell cycle, proliferation, apoptosis and metastasis, which were severally analyzed using propidium iodide (PI)-flow cytometry, 3-(4, 5-dimethylthiazol-2-y1)-2, 5-diphenyl tetrazolium bromide (MTT), Annexin V/PI-flow cytometry and transwell migration/invasion assays. ACAT2 and related proteins of cell cycle, epithelial-mesenchymal transition (EMT) were measured via western blot. Target relationship was analyzed via dual-luciferase reporter assay. A xenograft model was used to study circ_RPL23A action in mice. Results Both in CCRCC tissues and cells, circ_RPL23A had a down-regulated tendency. Explicitly, circ_RPL23A overexpression inhibited cell cycle, proliferation and metastasis but enhanced apoptosis of CCRCC cells, whereas these effects of circ_RPL23A were dependent on the suppression of its target miR-1233. Besides, miR-1233 could target ACAT2 and circ_RPL23A regulated ACAT2 by sponging miR-1233. Also importantly, miR-1233 was a pro-cancer gene in CCRCC via targeting ACAT2. CCRCC tumor growth was also decreased in vivo by circ_RPL23A through miR-1233/ACAT2 axis. Conclusion Altogether, the circ_RPL23A/miR-1233/ACAT2 axis in this report provides an in-depth cognition for CCRCC pathogenesis and circ_RPL23A may has pivotal value in diagnosing and treating CCRCC.