地奥司明治疗口腔鳞状细胞癌的潜在靶点及其生物信息学和转录谱分析

IF 2.1 4区 医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Steroids Pub Date : 2024-03-06 DOI:10.1016/j.steroids.2024.109393
Yang Xiao , Bingbing Xu , Xiaolan Li , Tianhao Ding , Wenxin Zhao , Xiaoxue Nie , Junxia Mu , Zhiyou Xiao , Qian Wang , Qunli Ren , Enkui Zhang
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引用次数: 0

摘要

薯蓣皂苷能抑制多种肿瘤细胞的增殖并导致其凋亡,而其对口腔鳞状细胞癌(OSCC)的抑制作用及其机制尚不清楚。本研究通过数据库预测了薯蓣皂苷治疗OSCC的靶点,然后对靶点进行了生物信息学分析,并进一步验证了薯蓣皂苷对OSCC细胞株HSC-3活性的影响、靶点的转录谱以及靶点与薯蓣皂苷的分子对接。结果显示,薯蓣皂苷治疗OSCC的潜在靶点有146个,涉及Ras、TNF、PI3K-AKT、HIF、NF-κB等信号通路,可通过细胞凋亡、自噬、增殖和分化、炎症反应、DNA修复等调控细胞活性。薯蓣皂苷能明显抑制 HSC-3 细胞的活性。AKT1、MET1、SRC1、APP1、CCND1、MYC、PTGS2、AR、NFKB1、BIRC2、MDM2、BCL2L1、MMP2等基因可能是薯蓣皂苷的重要作用靶点,它们不仅表达受薯蓣皂苷调控,而且其蛋白与薯蓣皂苷的结合能很高。这些结果表明,薯蓣皂苷可能通过AKT1、MMP2等靶点和多种信号通路对OSCC产生治疗作用,具有潜在的临床价值。
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Potential targets of diosgenin for the treatment of oral squamous cell carcinoma and their bioinformatics and transcriptional profiling analyses

Diosgenin can inhibit the proliferation and cause apoptosis of various tumor cells, and its inhibitory effect on oral squamous cell carcinoma (OSCC) and its mechanism are still unclear. In this study, we predicted the targets of diosgenin for the treatment of OSCC through the database, then performed bioinformatics analysis of the targets, and further verified the effect of diosgenin on the activity of OSCC cell line HSC-3, the transcriptional profile of the targets and the molecular docking of the targets with diosgenin. The results revealed that there were 146 potential targets of diosgenin for OSCC treatment, which involved signaling pathways such as Ras, TNF, PI3K-AKT, HIF, NF-κB, and could regulate cellular activity through apoptosis, autophagy, proliferation and differentiation, inflammatory response, DNA repair, etc. Diosgenin significantly inhibited HSC-3 cell activity. The genes such as AKT1, MET1, SRC1, APP1, CCND1, MYC, PTGS2, AR, NFKB1, BIRC2, MDM2, BCL2L1, MMP2, may be important targets of its action, not only their expression was regulated by diosgenin but also their proteins had a high binding energy with diosgenin. These results suggest that diosgenin may have a therapeutic effect on OSCC through AKT1, MMP2 and other targets and multiple signaling pathways, which is of potential clinical value.

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来源期刊
Steroids
Steroids 医学-内分泌学与代谢
CiteScore
5.10
自引率
3.70%
发文量
120
审稿时长
73 days
期刊介绍: STEROIDS is an international research journal devoted to studies on all chemical and biological aspects of steroidal moieties. The journal focuses on both experimental and theoretical studies on the biology, chemistry, biosynthesis, metabolism, molecular biology, physiology and pharmacology of steroids and other molecules that target or regulate steroid receptors. Manuscripts presenting clinical research related to steroids, steroid drug development, comparative endocrinology of steroid hormones, investigations on the mechanism of steroid action and steroid chemistry are all appropriate for submission for peer review. STEROIDS publishes both original research and timely reviews. For details concerning the preparation of manuscripts see Instructions to Authors, which is published in each issue of the journal.
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