Catechin-induced changes in PODXL, DNMTs, and miRNA expression in NALM6 cells: An integrated in silico and in vitro approach

Author:

Afgar Ali1,Keyhani Alireza2,Afgar Amirreza1,Mirzaei-Parsa Mohamad Javad3,Kermani Mahdiyeh Ramezani Zadeh1,Rezaei Masoud1,Ebrahimipour Mohammad1,Langroudi Ladan4,Bardsiri Mahla Sattarzadeh2,Vahidi Reza1

Affiliation:

1. Research Center for Hydatid Disease in Iran, Kerman University of Medical Sciences, Kerman, Iran, Iran, Islamic Republic Of

2. Kerman University of Medical Sciences

3. Department of Hematology and Medical Laboratory Sciences, Faculty of Allied Medicine, Kerman University of Medical Science, Iran

4. Department of Immunology, School of Medicine, Kerman University of Medical Sciences, Kerman, Iran

Abstract

Abstract

Background This study explored the impact of predicted miRNAs on DNA methyltransferases (DNMTs) and the PODXL gene in NALM6 cells, revealing the significance of these miRNAs in acute lymphocytic leukemia (ALL). Methods We employed a multifaceted approach comprising bioinformatic analyses (protein structure prediction, molecular docking, dynamics, ADMET study) and miRNA evaluations to explore the therapeutic effects of catechin compounds on DNMTs. Results Our evaluation revealed a nuanced relationship in which catechin treatment induced increased miRNA expression and decreased DNMT1 and DNMT3B levels in NALM6 cells. This indirect modulation impacted PODXL expression, contributing to cancer characteristics. Conclusion The overexpression of DNMT1 and DNMT3B in NALM6 cells may promote ALL development via a mechanism regulated by microRNAs, particularly miR-548 and miR-200c. Altered DNMT1 and DNMT3B expression is correlated with decreased miR-548 and miR-200c expression before and after catechin treatment, respectively, leading to the dysregulation of tumor suppressor genes, such as PODXL, and cancer cell characteristics. These findings underscore the therapeutic potential of catechin compounds targeting DNMTs and miRNAs in ALL treatment.

Publisher

Research Square Platform LLC

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