PARP1 regulates epigenetic processes through DNMT1 and UHRF1 in oxaliplatin-treated colon cancer cells.

Venhar Gurbuz Can; Tansu Kuşat

doi:10.19161/etd.1623604

EN TR

PARP1 regulates epigenetic processes through DNMT1 and UHRF1 in oxaliplatin-treated colon cancer cells.

Abstract

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.

Keywords

Oxaliplatin uygulanan kolon kanseri hücrelerinde PARP1, DNMT1 ve UHRF1 üzerinden epigenetik olayları düzenler

Öz

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.

Anahtar Kelimeler

Supporting Institution

yok

Project Number

yok

Ethical Statement

Hücre hattı çalışması olduğu için Etik onay alınmamıştır

Thanks

yok

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Details

Primary Language

English

Subjects

Cancer Genetics , Cancer Diagnosis , Chemotherapy , Molecular Targets , Predictive and Prognostic Markers

Journal Section

Research Article

Authors

Venhar Gurbuz Can ^*
0000-0002-9777-5173
Türkiye

Tansu Kuşat
0000-0001-7237-1562
Türkiye

Publication Date

December 8, 2025

Submission Date

January 20, 2025

Acceptance Date

July 6, 2025

Published in Issue

Year 2025 Volume: 64 Number: 4

DOI

https://doi.org/10.19161/etd.1623604

IZ

https://izlik.org/JA39TN59FK

Cite

RIS / Bibtex

Vancouver

1.Venhar Gurbuz Can, Tansu Kuşat. PARP1 regulates epigenetic processes through DNMT1 and UHRF1 in oxaliplatin-treated colon cancer cells. EJM. 2025 Dec. 1;64(4):612-20. doi:10.19161/etd.1623604