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.

Circ_0003146 upregulates SCARB1 expression by acting as a miR-1272 sponge to promote malignant behaviors of clear cell renal cell carcinoma

“…[29] asserted that circRNA_002178 enhanced tumor growth by targeting miR-328-3p to reduce the expression of COL1A1. CircRNA_103809 induced cancer-promoting function by mediating miR-4302-targeted ZNF121 level in lung cancer [30], and circ_RPL23A elevated the level of ACAT2 to retard cell progression by sequestering miR-1233 in ccRCC [31]. Our reverted assays indicated that SCARB1 attenuated the inhibitory regulation of circ_0003146 knockdown in ccRCC cells, which suggested that the oncogenic role of circ_003146 was achieved by upregulating SCARB1.…”

Circ_0037866 Contributes to the Tumorigenesis of Renal Cell Carcinoma by Sequestering miR-384 to Elevate Chromobox 5 Expression

“…Besides, circ-ITCH was demonstrated to perform anticancer effects in ccRCC by suppressing cell invasion and migration through the miR-106b-5p/PDCD4 axis [21]. Cheng et al [22] indicated circ_RPL23A overexpression led to cell cycle, proliferation, and metastasis arrest in ccRCC by upregulating ACAT2 through abolishing miR-1233. All the findings imply the emerging role of circRNA as a biomarker in RCC.…”

miR-1251-5p Overexpression Inhibits Proliferation, Migration, and Immune Escape in Clear Cell Renal Cell Carcinoma by Targeting NPTX2

“…e ccRCC has been the 13th commonly diagnosed cancer all over the world in 2020, which brings deep influence on human health [1]. At present, the biomarker study about ccRCC has made great progress, and micro-RNAs (miRNAs) are increasingly being discovered for having a function in the occupancy and growth of ccRCC [2]. miRNAs are a kind of noncoding RNAs with more than 20 nucleotides that have no potential to encode proteins [3].…”