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表没食子儿茶素没食子酸酯诱导 Nalm6 细胞中 PODXL、DNMTs 和 miRNA 表达的变化:一种综合的计算和体外方法。

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

机构信息

Research Center for Hydatid Disease in Iran, Kerman University of Medical Sciences, Kerman, Iran.

Leishmaniasis Research Center, Kerman University of Medical Sciences, Kerman, Iran.

出版信息

BMC Complement Med Ther. 2024 Jun 15;24(1):234. doi: 10.1186/s12906-024-04521-2.

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.

摘要

背景

本研究探讨了预测 miRNA 对 Nalm6 细胞中 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。

方法

采用综合方法,结合蛋白质结构预测、分子对接、动力学和 ADMET 分析等生物信息学分析,以及基因和 miRNA 表达模式的评估,来阐明表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。

结果

我们的研究结果表明,表儿茶素具有抑制 DNMT 酶的能力。这种抑制作用与 microRNAs miR-200c 和 miR-548 的上调以及 PODXL 基因表达的下调有关。这些分子相互作用导致 ALL (Nalm6) 细胞中凋亡反应增强。

结论

该研究表明,表儿茶素可能是诱导 ALL 细胞凋亡的一种可行的治疗方法。这是通过调节表观遗传机制和改变基因表达谱来实现的,突出了表儿茶素作为癌症治疗剂的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/163e/11179370/c03000eec01f/12906_2024_4521_Fig1_HTML.jpg

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