CircFOXM1 silencing represses cell proliferation, migration and invasion by regulating miR-515-5p/ADAM10 axis in prostate cancer

Abstract

Circular FOXM1 (circFOXM1) has been demonstrated to participate in the initiation and development of cancers, including prostate cancer (PCa). However, there is no relevant information on the regulation of PCa by circFOXM1. The RNA level of circFOXM1 was detected by qRT-PCR in PCa tissues and cells. The protein expression was performed by western blot and immunohistochemistry assay. Cell proliferation was examined by 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide, colony formation and flow cytometry assays. The abilities of cell migration and invasion were determined by transwell assay. The relationship between circFOXM1 and miR-515-5p or ADAM10 was predicted by starBaseV2.0 online database, and identified by dual-luciferase reporter assay or RNA pull-down assay. The effects of circFOXM1 silencing and ADAM10 knockdown on PCa growth in vivo were evaluated by in-vivo tumor formation assay. As a result, we found that circFOXM1 and ADAM10 expression were upregulated in PCa tissues and cells. Functional analysis showed that circFOXM1 silencing repressed proliferation, migration and invasion, and induced cell cycle arrest, whereas these effects were partly reversed by miR-515-5p inhibitor. Additionally, circFOXM1 directly sponged miR-515-5p, and miR-515-5p bound to ADAM10. ADAM10 absence also repressed PCa process. Furthermore, in-vivo tumor formation assay revealed that both circFOXM1 silencing and ADAM10 knockdown repressed tumor growth in vivo. Thus, we came a conclusion that circFOXM1 contributed to PCa progression via regulating miR-515-5p/ADAM10 axis. These results may provide a theoretical basis for further studying the progression of PCa.