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CircFOXM1 silencing represses cell proliferation, migration and invasion by regulating miR-515-5p/ADAM10 axis in
Gong-Xue Liu1, Tao Zheng, Yong Zhang
1Department of Urology, Wuhan Fourth Hospital, Puai Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China.
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.
Insights
Circular FOXM1 (circFOXM1) promotes prostate cancer (PCa) progression by upregulating ADAM10 via sponging miR-515-5p. Silencing circFOXM1 or ADAM10 inhibits PCa growth and metastasis, offering potential therapeutic targets.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Circular FOXM1 (circFOXM1) is implicated in various cancers.
- The specific role of circFOXM1 in prostate cancer (PCa) progression remained unclear.
- Understanding circFOXM1's regulatory mechanisms in PCa is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the role and regulatory mechanism of circFOXM1 in prostate cancer (PCa).
- To explore the relationship between circFOXM1, miR-515-5p, and ADAM10 in PCa.
- To evaluate the therapeutic potential of targeting the circFOXM1/miR-515-5p/ADAM10 axis in PCa.
Main Methods:
- Quantitative real-time PCR (qRT-PCR) and western blot to assess circFOXM1 and ADAM10 expression.
- Cell proliferation, migration, invasion, and cell cycle assays to evaluate functional impacts.
- Dual-luciferase reporter and RNA pull-down assays to confirm molecular interactions.
- In-vivo tumor formation assays to assess therapeutic efficacy.
Main Results:
- circFOXM1 and ADAM10 were significantly upregulated in PCa tissues and cells.
- circFOXM1 silencing inhibited PCa cell proliferation, migration, invasion, and induced cell cycle arrest.
- circFOXM1 directly sponged miR-515-5p, which in turn targeted ADAM10, forming the circFOXM1/miR-515-5p/ADAM10 axis.
- Inhibition of circFOXM1 or ADAM10 suppressed tumor growth in vivo.
Conclusions:
- circFOXM1 drives prostate cancer (PCa) progression through the miR-515-5p/ADAM10 pathway.
- circFOXM1 and ADAM10 represent potential therapeutic targets for PCa treatment.
- This study provides a theoretical basis for further research into PCa progression and treatment strategies.
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