探索分子靶点:宫颈癌治疗中的草药分离物。

Maryam Ahmadi, Razieh Abdollahi, Marzieh Otogara, Amir Taherkhani
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引用次数: 0

摘要

目的:宫颈癌(CxCa)是全球健康面临的重大挑战,在女性癌症相关死亡率中排名第四。虽然化疗方案在延长总生存期方面取得了逐步进展,但复发性宫颈癌患者的前景仍然令人沮丧。当务之急是探索创新的治疗途径,而分子靶向治疗则是一种前景广阔的候选疗法。之前的研究揭示了表儿茶素、姜黄素、没食子酸、药根碱和乔木碱这五种不同草药化合物对 CxCa 的治疗效果:方法:研究人员采用系统生物学方法鉴别 CxCa 组织中相对于健康宫颈上皮组织的差异表达基因(DEGs)。以与 CxCa 相关的基因为基础,构建了蛋白质-蛋白质相互作用网络(PPIN)。在 PPIN 中发现了中心基因,并通过 Kaplan-Meier 生存曲线探讨了其预后意义。对所选草药化合物与 CxCa 预后标志物主调节因子的结合亲和力进行了评估:结果:MYC、IL6、JUN、RRM2 和 VEGFA 的过表达与 CxCa 的不良预后之间存在明显的相关性。这些标志物的调控明显受到转录因子 CEBPD 的影响。分子对接分析表明,myricetin 与 CEBPD DNA 结合位点的结合亲和力很强:本文的研究结果揭示了在 CxCa 恶性转化过程中起核心作用的关键基因和通路。CEBPD 已成为利用 myricetin 治疗潜力的潜在靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Exploring molecular targets: herbal isolates in cervical cancer therapy.

Objective: Cervical cancer (CxCa) stands as a significant global health challenge, ranking fourth in cancer-related mortality among the female population. While chemotherapy regimens have demonstrated incremental progress in extending overall survival, the outlook for recurrent CxCa patients remains disheartening. An imperative necessity arises to delve into innovative therapeutic avenues, with molecular targeted therapy emerging as a promising candidate. Previous investigations have shed light on the therapeutic effectiveness of five distinct herbal compounds, epicatechin, curcumin, myricetin, jatrorrhizine, and arborinine, within the context of CxCa.

Methods: A systems biology approach was employed to discern differentially expressed genes (DEGs) in CxCa tissues relative to healthy cervical epithelial tissues. A protein-protein interaction network (PPIN) was constructed, anchored in the genes related to CxCa. The central genes were discerned within the PPIN, and Kaplan-Meier survival curves explored their prognostic significance. An assessment of the binding affinity of the selected herbal compounds to the master regulator of prognostic markers in CxCa was conducted.

Results: A significant correlation between the overexpression of MYC, IL6, JUN, RRM2, and VEGFA and an adverse prognosis in CxCa was indicated. The regulation of these markers is notably influenced by the transcription factor CEBPD. Molecular docking analysis indicated that the binding affinity between myricetin and the CEBPD DNA binding site was robust.

Conclusion: The findings presented herein have unveiled pivotal genes and pathways that play a central role in the malignant transformation of CxCa. CEBPD has emerged as a potential target for harnessing the therapeutic potential of myricetin in this context.

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