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Abstract：
This investigation delves into the influence of predicted microRNAs on DNA methyltransferases (DNMTs) and the PODXL gene within the NB4 cell line, aiming to elucidate their roles in the pathogenesis of acute myeloid leukemia (AML). A comprehensive methodological framework was adopted to explore the therapeutic implications of 6-gingerol on DNMTs. This encompassed a suite of bioinformatics tools for protein structure prediction, docking, molecular dynamics, and ADMET profiling, alongside empirical assessments of miRNA and PODXL expression levels. Such a multifaceted strategy facilitated an in-depth understanding of 6-gingerol\'s potential efficacy in DNMT modulation. The findings indicate a nuanced interplay where 6-gingerol administration modulated miRNA expression levels, decreasing in DNMT1 and DNMT3A expression in NB4 cells. This alteration indirectly influenced PODXL expression, contributing to the manifestation of oncogenic phenotypes. The overexpression of DNMT1 and DNMT3A in NB4 cells may contribute to AML, which appears modulable via microRNAs such as miR-193a and miR-200c. Post-treatment with 6-gingerol, DNMT1 and DNMT3A expression alterations were observed, culminating in the upregulation of miR-193a and miR-200c. This cascade effect led to the dysregulation of tumor suppressor genes in cancer cells, including downregulation of PODXL, and the emergence of cancerous traits. These insights underscore the therapeutic promise of 6-gingerol in targeting DNMTs and microRNAs within the AML context.
摘要：
这项研究探讨了预测的microRNA对NB4细胞系中DNA甲基转移酶（DNMT）和PODXL基因的影响，旨在阐明它们在急性髓系白血病（AML）发病机制中的作用。采用了全面的方法学框架来探索6-姜酚对DNMT的治疗意义。这包括一套用于蛋白质结构预测的生物信息学工具，对接,分子动力学,和ADMET分析，以及miRNA和PODXL表达水平的经验评估。这种多方面的策略有助于深入了解6-姜辣素在DNMT调制中的潜在功效。这些发现表明了一个微妙的相互作用，其中6-姜辣素给药调节miRNA表达水平，NB4细胞中DNMT1和DNMT3A表达降低。这种改变间接影响PODXL表达，有助于致癌表型的表现。DNMT1和DNMT3A在NB4细胞中的过表达可能有助于AML,似乎可通过miR-193a和miR-200c等microRNA进行调节。用6-姜酚后处理，观察到DNMT1和DNMT3A表达改变，最终导致miR-193a和miR-200c的上调。这种级联效应导致癌细胞中肿瘤抑制基因的失调，包括PODXL的下调，以及癌变特征的出现。这些见解强调了6-姜辣素在AML背景下靶向DNMT和microRNA的治疗前景。
