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

IF 3.3 2区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE
Ali Afgar, Alireza Keyhani, Amirreza Afgar, Mohamad Javad Mirzaei-Parsa, Mahdiyeh Ramezani Zadeh Kermani, Masoud Rezaei, Mohammad Ebrahimipour, Ladan Langroudi, Mahla Sattarzadeh Bardsiri, Reza Vahidi
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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: 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.

Results: 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.

Conclusion: 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.

儿茶素诱导 Nalm6 细胞中 PODXL、DNMTs 和 miRNA 表达的变化:一种综合的硅学和体外方法。
背景:这项研究探讨了Nalm6细胞中预测的miRNA对DNA甲基转移酶(DNMTs)和PODXL基因的影响,揭示了这些miRNA在急性淋巴细胞白血病(ALL)中的重要性:采用了一种综合方法,将包括蛋白质结构预测、分子对接、动力学和 ADMET 分析在内的生物信息学分析与基因和 miRNA 表达模式的评估结合起来。我们采用这种方法来阐明儿茶素化合物在调节 DNA 甲基转移酶(DNMTs)和 PODXL 基因活性方面的治疗潜力:我们的研究结果表明,儿茶素具有抑制 DNMT 酶的能力。这种抑制作用与 microRNAs miR-200c 和 miR-548 的上调以及 PODXL 基因表达的同时下调有关。这些分子相互作用最终增强了 ALL(Nalm6)细胞的凋亡反应:本研究认为,儿茶素可能是诱导 ALL 细胞凋亡的可行治疗途径。这是通过调节表观遗传机制和改变基因表达谱来实现的,凸显了儿茶素作为癌症治疗药物的潜力。
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来源期刊
BMC Complementary Medicine and Therapies
BMC Complementary Medicine and Therapies INTEGRATIVE & COMPLEMENTARY MEDICINE-
CiteScore
6.10
自引率
2.60%
发文量
300
审稿时长
19 weeks
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