Circ_0002623 promotes bladder cancer progression by regulating the miR-1276/SMAD2 axis

Cancer Sci. 2022 Apr;113(4):1250-1263. doi: 10.1111/cas.15274. Epub 2022 Mar 3.

ABSTRACT

Circular RNAs (circRNAs) are key regulatory factors in the development of multiple cancers. This study is targeted at exploring the effect of circ_0002623 on bladder cancer (BCa) progression and its mechanism. Circ_0002623 was screened out by analyzing the expression profile of circRNAs in BCa tissues. Circ_0002623, miR-1276, and SMAD2 mRNA expression levels in clinical sample tissues and cell lines were detected through quantitative real-time polymerase chain reaction (qRT-PCR). After circ_0002623 had been overexpressed or silenced in BCa cells, the cell proliferation, migration, and cell cycle were evaluated by CCK-8, BrdU, Transwell assay, and flow cytometry. Tumor xenograft model was used to validate the biological function of circ_0002623 in vivo. Bioinformatics analysis and dual-luciferase reporter gene assay were conducted for analyzing and confirming, respectively, the targeted relationship between circ_0002623 and miR-1276, as well as between miR-1276 and SMAD2. The regulatory effects of circ_0002623 and miR-1276 on the expression levels of TGF-β, WNT1, and SMAD2 in BCa cells were detected by Western blot. We reported that, in BCa tissues and cell lines, circ_0002623 was upregulated, whereas miR-1276 was downregulated. Circ_0002623 positively regulated BCa cell proliferation, migration, and cell cycle progression. Additionally, circ_0002623 could competitively bind with miR-1276 to increase the expression of SMAD2, the target gene of miR-1276. Furthermore, circ_0002623 could regulate the expression of TGF-β and WNT1 via modulating miR-1276 and SMAD2. This study helps to better understand the molecular mechanism underlying BCa progression.

PMID:35048477 | PMC:PMC8990873 | DOI:10.1111/cas.15274