Gulia Shweta, Chandra Prakash, Das Asmita
Department of Biotechnology, Delhi Technological University, Main Bawana Road, Delhi, 110042, India.
Curr Comput Aided Drug Des. 2025;21(5):609-628. doi: 10.2174/0115734099279130231211053542.
The study aimed to explore the crucial genes involved in cancer-related biological processes, including EMT, autophagy, apoptosis, anoikis, and metastasis. It also sought to identify common genes among the pathways linked to these biological processes, determine the level of Bcl-2 expression in various types of cancers, and find a potent inhibitor of Bcl-2 among natural compounds.
Common genes involved in the pathways related to EMT, autophagy, apoptosis, anoikis, and metastasis were explored, and the level of the most frequently overexpressed gene that was Bcl-2, in various types of cancers was analyzed by gene expression analysis. A set of 102 natural compounds was sorted according to their docking scores using molecular docking and filtering. The top-ranked molecule was chosen for additional molecular dynamics (MD) simulation for 100 ns. Differential gene expression analysis was performed for Dioscin using GEO2R.
The study identified four common genes, Bcl-2, Bax, BIRC3, and CHUK, among the pathways linked to EMT, autophagy, apoptosis, anoikis, and metastasis. Bcl-2 was highly overexpressed in many cancers, including Acute Myeloid Leukemia, Diffuse large B cell lymphoma, and Thymoma. The Dioscin structure in the Bcl-2 binding site received the highest docking score and the most relevant interactions. Dioscin's determined binding free energy by MM/GBSA was -52.21 kcal/mol, while the same calculated by MM/PBSA was -9.18 kcal/mol. A p-value of less than 0.05 was used to determine the statistical significance of the analysis performed using GEO2R. It was observed that Dioscin downregulates Bcl-2, BIRC3, and CHUK and upregulates the pro-apoptotic protein Bax.
The study concluded that Dioscin has the potential to act as a protein inhibitor, with a noteworthy value of binding free energy and relevant interactions with the Bcl-2 binding site. Dioscin might be a good alternative for targeting multiple cancer pathways through a single target.
本研究旨在探索参与癌症相关生物学过程的关键基因，包括上皮-间质转化（EMT）、自噬、凋亡、失巢凋亡和转移。研究还试图识别与这些生物学过程相关途径中的共同基因，确定不同类型癌症中Bcl-2的表达水平，并在天然化合物中找到一种有效的Bcl-2抑制剂。
探索参与EMT、自噬、凋亡、失巢凋亡和转移相关途径的共同基因，并通过基因表达分析来分析各种类型癌症中最常过度表达的基因即Bcl-2的水平。使用分子对接和筛选，根据102种天然化合物的对接分数对它们进行排序。选择排名最高的分子进行100纳秒的额外分子动力学（MD）模拟。使用GEO2R对薯蓣皂苷进行差异基因表达分析。
该研究在与EMT、自噬、凋亡、失巢凋亡和转移相关的途径中鉴定出四个共同基因，即Bcl-2、Bax、BIRC3和CHUK。Bcl-2在许多癌症中高度过度表达，包括急性髓性白血病、弥漫性大B细胞淋巴瘤和胸腺瘤。薯蓣皂苷在Bcl-2结合位点的结构获得了最高的对接分数和最相关的相互作用。通过MM/GBSA计算的薯蓣皂苷的结合自由能为-52.21千卡/摩尔，而通过MM/PBSA计算的相同值为-9.18千卡/摩尔。使用小于0.05的p值来确定使用GEO2R进行的分析的统计学意义。观察到薯蓣皂苷下调Bcl-2、BIRC3和CHUK，并上调促凋亡蛋白Bax。
该研究得出结论，薯蓣皂苷有潜力作为一种蛋白抑制剂，具有值得注意的结合自由能值以及与Bcl-2结合位点的相关相互作用。薯蓣皂苷可能是通过单一靶点靶向多种癌症途径的良好选择。
