IRF5 inhibits prostate cancer metastasis and drug resistance by decreasing CXCR4/CXCL12 complex

Year 2021, Volume: 46 Issue: 4, 1632 - 1639, 30.12.2021

Burcin Abas Nesrin Büyükkarıncalı Ozge Cevik

Abstract

Purpose: Prostate cancer is the most common type of cancer in men, and drug resistance is typical in its treatment. Chemokines especially play a role in tumor growth and drug resistance mechanisms. IRF5 is a critical transcription factor in immune response, and its relationship with the chemokine family CXCR4 and CXCL12 was investigated in this study.
Materials and Methods: The pIRF5 plasmid was transfected in an androgen-independent human prostate cancer cell line (PC3), and the IRF5 protein was overexpressed. CXCR4 and CXCL12 protein expression levels were determined by western blot and gene expression levels by the qPCR method. In addition, colony formation was examined in cells after IRF5 transfection, and CXCL12 secretion was measured in cell media.
Results: Cell viability and colony formation were found to be significantly reduced in IRF5 transfected PC3 cells. In addition, CXCR4 and CXCL12 protein expression and gene expression levels of IRF5 transfected cells were found to be significantly decreased.
Conclusion: This study shows that IRF5, a transcription factor, affects CXCR4/CXCL12, which is involved in microenvironment-mediated metastasis developing in prostate cancer. Thus, in the treatment of prostate cancer, IRF5 gene therapy can prevent metastasis and offer essential contributions to newly developed treatment methods in this regard.

Keywords

IRF5, Prostate cancer, CXCR4, CXCL12, chemokines

Supporting Institution

Adnan Menderes University Research Grant Projects

Project Number

TPF-19021

Thanks

This work was supported by the Adnan Menderes University Research Grant Projects (TPF-19021) and by a grant (214Z057) from the Scientific and Technological Research Council of Turkey (TUBITAK) to Dr. Ozge Cevik.

IRF5, CXCR4/CXCL12 kompleksini azaltarak prostat kanseri metastazını ve ilaç direncini inhibe eder

Abstract

Amaç: Prostat kanseri erkeklerde en sık görülen kanser türüdür ve tedavisinde ilaç direnci tipiktir. Kemokinler özellikle tümör büyümesinde ve ilaç direnç mekanizmalarında rol oynarlar. IRF5, immün yanıtta kritik bir transkripsiyon faktörüdür ve bu çalışmada kemokin ailesi CXCR4 ve CXCL12 ile ilişkisi araştırılmıştır.
Gereç ve Yöntem: pIRF5 plazmidi, androjenden bağımsız bir insan prostat kanseri hücre hattında (PC3) transfekte edildi ve IRF5 proteini aşırı eksprese edildi. CXCR4 ve CXCL12 protein ekspresyon seviyeleri western blot ve gen ekspresyon seviyeleri ile qPCR yöntemi ile belirlendi. Ek olarak, IRF5 transfeksiyonundan sonra hücrelerde koloni oluşumu incelendi ve hücre ortamında CXCL12 sekresyonu ölçüldü.
Bulgular: IRF5 ile transfekte edilmiş PC3 hücrelerinde hücre canlılığı ve koloni oluşumunun önemli ölçüde azaldığı bulundu. Ek olarak, IRF5 ile transfekte edilmiş hücrelerin CXCR4 ve CXCL12 protein ekspresyonu ve gen ekspresyon seviyelerinin önemli ölçüde azaldığı tespit edildi.
Sonuç: Bu çalışma, bir transkripsiyon faktörü olan IRF5'in prostat kanserinde gelişen mikroçevre aracılı metastazda yer alan CXCR4/CXCL12'yi etkilediğini göstermektedir. Böylece prostat kanseri tedavisinde IRF5 gen tedavisi metastazı önleyebilir ve bu konuda yeni geliştirilen tedavi yöntemlerine önemli katkılar sunabilir.

Keywords

IRF5, Prostat kanseri, CXCR4, CXCL12, kemokinler

Project Number

TPF-19021

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