ejm Ege Tıp Dergisi 1016-9113 2147-6500 Ege University 10.19161/etd.1623604 Cancer Genetics Cancer Diagnosis Chemotherapy Molecular Targets Predictive and Prognostic Markers Kanser Genetiği Kanser Tanısı Kemoterapi Moleküler Hedefler Öngörücü ve Prognostik Belirteçler PARP1 regulates epigenetic processes through DNMT1 and UHRF1 in oxaliplatin-treated colon cancer cells. Oxaliplatin uygulanan kolon kanseri hücrelerinde PARP1, DNMT1 ve UHRF1 üzerinden epigenetik olayları düzenler https://orcid.org/0000-0002-9777-5173 Gurbuz Can Venhar KARABÜK ÜNİVERSİTESİ, TIP FAKÜLTESİ https://orcid.org/0000-0001-7237-1562 Kuşat Tansu KARABÜK ÜNİVERSİTESİ, TIP FAKÜLTESİ 12 08 2025 64 4 612 620 01 20 2025 07 06 2025 Copyright © 1962, Ege Journal of Medicine 1962 Ege Journal of Medicine

Aim: Colon cancer is the second most commonly diagnosed cancer among females and the third most frequently diagnosed cancer among males worldwide. Epigenetics is described as alterations in gene expression without changes in nucleotide sequence. Epigenetic mechanisms can modulate the activation or inactivation of cancer-associated genes. The aim of our study was to demonstrate the epigenetic effect of PARP1, DNMT1, and UHRF1 genes in oxaliplatin-treatment colon cancer cell line. Materials and Methods: HT-29 cells were cultured in suitable medium. Then, when the cells were grown up to a certain number, oxaliplatin was applied for 24, 48, and 72 hours at doses of 2.5, 5, 10, 25, 50, 100, and 200 µM to the HT-29 cells, and Cell viability was detected by XTT test. Following the completion of the XTT test, PARP1, DNMT1, and UHRF1 gene expression levels were analyzed by the real-time PCR method. Results: Our results revealed that Oxaliplatin significantly suppressed the expression of UHRF1 and DNMT1 in colon cancer cells, whereas it significantly stimulated the expression of PARP1.Conclusion: In conclusion, the data obtained indicates that the UHRF1, PARP1 and DNMT1 genes may function as modulators of the epigenome and that DNMT1 and UHRF1 interact negatively with PARP1. This study has demonstrated the potential of the UHRF1, PARP1 and DNMT1 genes as targets for colon cancer treatment and as candidate biomarkers.

Amaç: Kolon kanseri dünya genelinde kadınlarda en sık görülen ikinci, erkeklerde ise en sık görülen üçüncü kanser türüdür. Epigenetik, nükleotid diziliminde değişiklik olmaksızın gen ifadesinde meydana gelen değişiklikler olarak tanımlanmaktadır. Kanserle ilişkili genlerin aktivasyonu veya inaktivasyonu epigenetik mekanizmalarla modüle edilebilmektedir. Çalışmamızın amacı, oksaliplatin ile tedavi edilen kolon kanseri hücre hattında PARP1, DNMT1 ve UHRF1 genlerinin epigenetik etkisini gösterebilmektir. Gereç ve Yöntem: HT-29 hücreleri uygun besiyeri ortamında kültüre edilmiş, daha sonra, belirli bir sayıya kadar büyütüldüğünde, hücrelere 2.5, 5, 10, 25, 50, 100, 200 µM dozlarında ve 24, 48 ve 72 saat boyunca oksaliplatin uygulanmıştır. Uygulama sonrasında, hücre canlılığı XTT yöntemi ile tespit edilmiştir. XTT yönteminin tamamlanmasını takiben, PARP1, DNMT1 ve UHRF1 genlerinin ekspresyon seviyeleri gerçek zamanlı PCR yöntemi ile analiz edilmiştir. Bulgular: Oxaliplatinin kolon kanseri hücrelerinde UHRF1 ve DNMT1 ekspresyonunu önemli ölçüde baskıladığını, PARP1 ekspresyonunu ise önemli ölçüde uyardığını ortaya koymuştur. Sonuç: Elde ettiğimiz veriler ışığında UHRF1, PARP1ve DNMT1 genlerinin epigenomun bir modülatörü olarak işlev görebileceğini ve DNMT1 ve UHRF1 genlerinin PARP1geni ile negatif korelasyon gösterdiğini tespit ettik. Bu çalışma, UHRF1, PARP1 ve DNMT1'in kolon kanseri tedavileri için potansiyel hedef ve aday biyobelirteçler olarak belirlenebileceğini göstermiştir.

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