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Study of the effect of sFRP1 protein on molecules involved in the regulation of DNA methylation in CML cell line

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Abstract

Wnt-signaling pathway plays a crucial role in the pathogenesis and progression of Chronic Myeloid Leukemia (CML). sFRP1 is involved in the suppression of the Wnt-signaling pathway and has been shown to be epigenetically silenced by promoter hypermethylation during CML progression. DNMT3A plays a crucial role in promoter hypermethylation and is responsible for establishing methylation patterns. We aimed to analyze the relationship between sFRP1 expression and DNMT3A, TET1, TET2 and TET3 proteins that are responsible for maintaining cellular methylation patterns; along with miRNAs miR144-3p and miR-767-5p that are known to be associated with these proteins. CML cell lines K562 and K562S which stably expresses sFRP1, were used to compare the changes in miR144-3p and miR-767-5p expression. DNMT3A, TET1, TET2 and TET3 protein levels were analyzed by Western blot. In K562S cells the expression of miR-144-3p and miR-767-5p were decreased along with DNMT3A and TET1 protein levels. On the contrary, TET2 protein was increased. Our results support other reports involving sFRP1 and methylation dynamics; as well as opening new avenues of exploration. Our data supports the conclusion that re-expression of sFRP1 protein alters the expression of factors that play important roles in the overall methylation patterns in the leukemic cell line K562.

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Funding

Financial support was provided by Dokuz Eylül University Department of Scientific Research Projects (Project numbers: TSA-2023–3218 and 2021.KB.SAG.058).

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Authors and Affiliations

  1. Department of Medical Biology and Genetics, Dokuz Eylul University Faculty of Medicine, Inciralti, 35340, Izmir, Turkey

    Nazli Demirkiran, Bengusu Aydin, Zeynep Yuce & H. Ogun Sercan

  2. Department of Medical Laboratory Techniques, Izmir Katip Celebi University, Vocational School of Health Services, Izmir, Turkey

    Melek Pehlivan

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  1. Nazli Demirkiran
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Contributions

This study was designed by all authors contributions equally. Experimental process conducted by Nazli DEMIRKIRAN and Bengusu AYDIN. Results analyzed under the supervision of Melek PEHLIVAN, Zeynep YUCE and H. Ogun SERCAN. Writing and editing of the paper done by Nazli DEMIRKIRAN. Paper reviewed by H. Ogun SERCAN and Zeynep YUCE.

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Correspondence to H. Ogun Sercan.

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The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Dokuz Eylul University (2020/29–22).

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Demirkiran, N., Aydin, B., Pehlivan, M. et al. Study of the effect of sFRP1 protein on molecules involved in the regulation of DNA methylation in CML cell line. Med Oncol 41, 109 (2024). https://doi.org/10.1007/s12032-024-02336-2

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