مطالعه فارماکولوژی شبکه‌ای از مسیرهای سیگنال‌دهی و ژنهای هدف ماده بربرین در درمان سرطان تخمدان با استفاده از تجزیه و تحلیل بیوانفورماتیکی
محورهای موضوعی : فصلنامه زیست شناسی جانوریساناز پناهی آلانق 1 , یاسمن خمینه 2 , محمود تلخابی 3
1 - گروه علوم جانوری و زیست شناسی دریا، دانشکده علوم و فناوری زیستی، دانشگاه شهید بهشتی، تهران، ایران
2 - گروه علوم جانوری و زیست شناسی دریا، دانشکده علوم و فناوری زیستی، دانشگاه شهید بهشتی، تهران، ایران
3 - گروه علوم جانوری و زیست شناسی دریا، دانشکده علوم و فناوری زیستی، دانشگاه شهید بهشتی، تهران، ایران
کلید واژه: سرطان تخمدان, بربرین, فارماکولوژی شبکه, DEGs, شبکه برهمکنش پروتئین-پروتئین,
چکیده مقاله :
سرطان تخمدان یکی از بیماری‌های کشنده در زنان می‌باشد که تشخیص زودهنگام آن مشکل است. بنابراین، نیاز فوری به عوامل شیمیایی وجود دارد که می‌تواند در کنترل توسعه سرطان تخمدان کمک کند. بربرین، به عنوان یک ماده شیمیایی، دارای خواص آنتی اکسیدانی و دارویی متعددی است و نقش ضد سرطانی این ماده تحت پژوهش قرار دارد. هدف این مطالعه تجزیه و تحلیل ژنهای هدف بربرین در سرطان تخمدان و شناخت مسیرهای سیگنال‌دهی بربرین با استفاده از فارماکولوژی شبکه است. در این مطالعه، مجموعه داده GSE36668 از پایگاه داده GEO گرفته شد. ژنهای دارای بیان افتراقی(DEGs)، توسط GEO2R با 05/0 adj Pvalue < و 2≤∣logFC∣ مورد تجزیه و تحلیل قرار گرفت. اهداف مرتبط با بربرین از پایگاه‌های داده SwissTargetPrediction و Pharm Mapper جمع‌آوری شدند. شبکه برهمکنش پروتئین-پروتئین (PPI) اهداف مشترک بربرین و DEGs، بر اساس داده‌های موجود در پایگاه داده String و با استفاده از نرم‌افزار Cytoscape ترسیم شد. ژن‌هاي مشترك در بربرین و سرطان تخمدان، در بررسی مسیرهاي زیستی (BP) و مولکولی (MF) و سلولی استفاده شدند. 10 ژن هاب انتخابی در این مطالعه شامل ESR1، STAT1، CDK1، RXRA، PIK3CA، PGR، CCNB1، CHEK1، PIK3R1 و PIK3CG بودند. همچنین مشخص شد ژنهای هدف بربرین می‌توانند در مسیرهاي سیگنال‌دهی سرطان، سرطان زایی شیمیایی، تنش برشی سیال و آترواسکلروز، بلوغ تخمک با واسطه پروژسترون و مسیر سیگنالینگ PPAR، نقش داشته باشند. بر اساس این یافته‌ها بربرین می‌تواند بر بیان ژن‌هاي موثر در سرطان تخمدان و محصولات پروتئینی آن‌ها اثر داشته و با اثر بر مسیرهاي زیستی دخیل در این بیماری، راهکار مناسبی براي درمان سرطان تخمدان باشد.
Ovarian cancer is one of the fatal diseases in women, which is difficult to diagnose early. Therefore, there is an urgent need for chemical agents that can help control the development of ovarian cancer. Berberine, as a chemical substance, has many antioxidant and medicinal properties, and the anti-cancer role of this substance is under research. This study aims to analyze berberine target genes in ovarian cancer and to identify berberine signaling pathways using network pharmacology. In this study, the dataset GSE36668 was taken from the GEO database. Differentially expressed genes (DEGs) were analyzed by GEO2R with adj p < 0.05 and ∣logFC∣ ≤ 2. Berberine-related targets were collected from SwissTargetPrediction and Pharm Mapper databases. The protein-protein interaction (PPI) network of berberine common targets and DEGs was drawn based on the data in the String database and using Cytoscape software. Common genes in berberine and ovarian cancer were used to investigate biological (BP), molecular (MF), and cellular pathways. The 10 hub genes selected in this study included ESR1, STAT1, CDK1, RXRA, PIK3CA, PGR, CCNB1, CHEK1, PIK3R1, and PIK3CG. It was also found that berberine target genes can play a role in cancer signaling pathways, chemical carcinogenesis, fluid shear stress and atherosclerosis, progesterone-mediated oocyte maturation, and PPAR signaling pathway. Based on these findings, berberine can affect the expression of genes that are effective in ovarian cancer and their protein products, and by affecting the biological pathways involved in this disease, it is a suitable solution for the treatment of ovarian cancer.
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