Catechin-Induced changes in PODXL, DNMTs, and miRNA expression in Nalm6 cells: an integrated in silico and in vitro approach

• Published in: BMC complementary and alternative medicine 2024-06, Vol.24 (1), p.234-18
• Main Authors: Afgar, Ali, Keyhani, Alireza, Afgar, Amirreza, Mirzaei-Parsa, Mohamad Javad, Kermani, Mahdiyeh Ramezani Zadeh, Rezaei, Masoud, Ebrahimipour, Mohammad, Langroudi, Ladan, Bardsiri, Mahla Sattarzadeh, Vahidi, Reza
• Format: Article
• Language: English
• Subjects: Acute lymphoblastic leukemia; ALL; Amino acids; Analysis; Apoptosis; Apoptosis - drug effects; Bioinformatics; Bone marrow; Cancer; Cancer therapies; Catechin; Catechin - analogs & derivatives; Catechin - pharmacology; Cell growth; Cell Line, Tumor; Computer Simulation; Deoxyribonucleic acid; DNA; DNA fingerprinting; DNA methylation; DNA Modification Methylases - metabolism; Docking; Dynamic structural analysis; Energy; Enzyme inhibitors; Epigenetic inheritance; Epigenetics; Gene expression; Genes; Health aspects; Humans; Investigations; Leukemia; Lymphatic leukemia; MD simulation; Medical prognosis; Metabolism; Metastasis; Methods; Methyltransferase; Methyltransferases; MicroRNA; MicroRNAs; MicroRNAs - genetics; miRNA; miRNAs; Molecular docking; Molecular Docking Simulation; Molecular dynamics; Molecular interactions; Molecular structure; Pharmacology; PODXL; Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy; Predictions; Protein structure; Protein structure prediction; Proteins
• ISSN: 2662-7671; 2662-7671; 1472-6882
• DOI: 10.1186/s12906-024-04521-2

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). A comprehensive approach was adopted, integrating bioinformatic analyses encompassing protein structure prediction, molecular docking, dynamics, and ADMET profiling, in conjunction with evaluations of gene and miRNA expression patterns. This methodology was employed to elucidate the therapeutic potential of catechin compounds in modulating the activity of DNA methyltransferases (DNMTs) and the PODXL gene. The findings from our investigation indicate that catechins possess the capability to inhibit DNMT enzymes. This inhibitory effect is associated with the upregulation of microRNAs miR-200c and miR-548 and a concurrent downregulation of PODXL gene expression. These molecular interactions culminate in an augmented apoptotic response within ALL (Nalm6) cells. The study posits that catechins may represent a viable therapeutic avenue for inducing apoptosis in ALL cells. This is achieved through the modulation of epigenetic mechanisms and alterations in gene expression profiles, highlighting the potential of catechins as agents for cancer therapy.