fa تعیین مکانیسم های مولکولی تنظیم شده توسط ژن های RAD51 و MRE11 در بلوغ تخمک با استفاده از مطالعات بیوانفورماتیکی زیست شناسی Biology پژوهشي Original article <div style="text-align: justify;"><span style="font-size:11pt"><span style="line-height:115%"><span style="direction:rtl"><span style="unicode-bidi:embed"><span style="font-family:Calibri,sans-serif"><b><span lang="AR-SA" style="font-size:12.0pt"><span style="line-height:115%"><span b="" nazanin="" style="font-family:">مقدمه:</span></span></span></b><span lang="AR-SA" style="font-size:12.0pt"><span style="line-height:115%"><span b="" nazanin="" style="font-family:"> ناباروری زنان یکی از چالش‌های مهم سلامت باروری است و عوامل ژنتیکی و مولکولی متعددی در بروز آن نقش دارند. این مطالعه با هدف بررسی نقش ژن‌های</span></span></span><span dir="LTR" style="font-size:12.0pt"><span style="line-height:115%"><span new="" roman="" style="font-family:" times=""> RAD51 </span></span></span><span lang="AR-SA" style="font-size:12.0pt"><span style="line-height:115%"><span b="" nazanin="" style="font-family:">و</span></span></span><span dir="LTR" style="font-size:12.0pt"><span style="line-height:115%"><span new="" roman="" style="font-family:" times=""> MRE11 </span></span></span><span lang="AR-SA" style="font-size:12.0pt"><span style="line-height:115%"><span b="" nazanin="" style="font-family:">در بلوغ تخمک انجام گرفت</span></span></span><span dir="LTR" style="font-size:12.0pt"><span style="line-height:115%"><span new="" roman="" style="font-family:" times="">.</span></span></span></span></span></span></span></span><br> <span style="font-size:11pt"><span style="line-height:115%"><span style="direction:rtl"><span style="unicode-bidi:embed"><span style="font-family:Calibri,sans-serif"><b><span lang="AR-SA" style="font-size:12.0pt"><span style="line-height:115%"><span b="" nazanin="" style="font-family:">روش بررسی:</span></span></span></b><span lang="AR-SA" style="font-size:12.0pt"><span style="line-height:115%"><span b="" nazanin="" style="font-family:"> شبکه تعاملی پروتئین</span></span></span><span lang="AR-SA" style="font-size:12.0pt"><span style="line-height:115%"><span new="" roman="" style="font-family:" times="">&ndash;</span></span></span><span lang="AR-SA" style="font-size:12.0pt"><span style="line-height:115%"><span b="" nazanin="" style="font-family:">پروتئین از پایگاه </span></span></span><span dir="LTR" style="font-size:12.0pt"><span style="line-height:115%"><span new="" roman="" style="font-family:" times="">STRING</span></span></span><span lang="AR-SA" style="font-size:12.0pt"><span style="line-height:115%"><span b="" nazanin="" style="font-family:"> استخراج و تحلیل‌های شبکه‌ای در نرم‌افزار </span></span></span><span dir="LTR" style="font-size:12.0pt"><span style="line-height:115%"><span new="" roman="" style="font-family:" times="">Cytoscape</span></span></span><span lang="AR-SA" style="font-size:12.0pt"><span style="line-height:115%"><span b="" nazanin="" style="font-family:"> انجام گردید. برای شناسایی کلاسترهای عملکردی از الگوریتم </span></span></span><span dir="LTR" style="font-size:12.0pt"><span style="line-height:115%"><span new="" roman="" style="font-family:" times="">MCODE</span></span></span><span lang="AR-SA" style="font-size:12.0pt"><span style="line-height:115%"><span b="" nazanin="" style="font-family:"> و برای تحلیل مسیرهای زیستی از ابزارهای غنی‌سازی مسیر استفاده شد. بررسی </span></span></span><span dir="LTR" style="font-size:12.0pt"><span style="line-height:115%"><span new="" roman="" style="font-family:" times="">miRNA</span></span></span><span lang="AR-SA" style="font-size:12.0pt"><span style="line-height:115%"><span b="" nazanin="" style="font-family:">های تنظیم‌کننده نیز با استفاده از پایگاه </span></span></span><span dir="LTR" style="font-size:12.0pt"><span style="line-height:115%"><span new="" roman="" style="font-family:" times="">miRTarBase</span></span></span><span lang="AR-SA" style="font-size:12.0pt"><span style="line-height:115%"><span b="" nazanin="" style="font-family:"> صورت گرفت.</span></span></span></span></span></span></span></span><br> <span style="font-size:11pt"><span style="line-height:115%"><span style="direction:rtl"><span style="unicode-bidi:embed"><span style="font-family:Calibri,sans-serif"><b><span lang="AR-SA" style="font-size:12.0pt"><span style="line-height:115%"><span b="" nazanin="" style="font-family:">&nbsp;نتایج:</span></span></span></b><span lang="AR-SA" style="font-size:12.0pt"><span style="line-height:115%"><span b="" nazanin="" style="font-family:"> تحلیل شبکه نشان داد ژن‌های </span></span></span><span dir="LTR" style="font-size:12.0pt"><span style="line-height:115%"><span new="" roman="" style="font-family:" times="">BRCA1</span></span></span><span lang="AR-SA" style="font-size:12.0pt"><span style="line-height:115%"><span b="" nazanin="" style="font-family:"> و </span></span></span><span dir="LTR" style="font-size:12.0pt"><span style="line-height:115%"><span new="" roman="" style="font-family:" times="">BARD1</span></span></span><span lang="AR-SA" style="font-size:12.0pt"><span style="line-height:115%"><span b="" nazanin="" style="font-family:"> به‌عنوان گره‌های مرکزی عمل می‌کنند و براساس الگوریتم </span></span></span><span dir="LTR" style="font-size:12.0pt"><span style="line-height:115%"><span new="" roman="" style="font-family:" times="">MCODE</span></span></span><span lang="AR-SA" style="font-size:12.0pt"><span style="line-height:115%"><span b="" nazanin="" style="font-family:"> ژن‌های </span></span></span><span dir="LTR" style="font-size:12.0pt"><span style="line-height:115%"><span new="" roman="" style="font-family:" times="">ATM</span></span></span><span lang="AR-SA" style="font-size:12.0pt"><span style="line-height:115%"><span b="" nazanin="" style="font-family:"> و </span></span></span><span dir="LTR" style="font-size:12.0pt"><span style="line-height:115%"><span new="" roman="" style="font-family:" times="">ATRX</span></span></span><span lang="AR-SA" style="font-size:12.0pt"><span style="line-height:115%"><span b="" nazanin="" style="font-family:"> در کلاسترهای عملکردی مهم شناسایی شدند. مسیرهای زیستی به‌دست‌آمده نشان‌دهنده مشارکت این ژن‌ها در مسیرهایی همچون </span></span></span><span dir="LTR" style="font-size:12.0pt"><span style="line-height:115%"><span new="" roman="" style="font-family:" times="">Homologous Recombination</span></span></span><span lang="AR-SA" style="font-size:12.0pt"><span style="line-height:115%"><span b="" nazanin="" style="font-family:">، پاسخ به آسیب </span></span></span><span dir="LTR" style="font-size:12.0pt"><span style="line-height:115%"><span new="" roman="" style="font-family:" times="">DNA</span></span></span><span lang="AR-SA" style="font-size:12.0pt"><span style="line-height:115%"><span b="" nazanin="" style="font-family:">، </span></span></span><span dir="LTR" style="font-size:12.0pt"><span style="line-height:115%"><span new="" roman="" style="font-family:" times="">senescence</span></span></span><span lang="AR-SA" style="font-size:12.0pt"><span style="line-height:115%"><span b="" nazanin="" style="font-family:"> سلولی و چرخه سلولی بود. همچنین نتایج </span></span></span><span dir="LTR" style="font-size:12.0pt"><span style="line-height:115%"><span new="" roman="" style="font-family:" times="">miRTarBase</span></span></span><span lang="AR-SA" style="font-size:12.0pt"><span style="line-height:115%"><span b="" nazanin="" style="font-family:"> نشان داد چندین </span></span></span><span dir="LTR" style="font-size:12.0pt"><span style="line-height:115%"><span new="" roman="" style="font-family:" times="">miRNA</span></span></span><span lang="AR-SA" style="font-size:12.0pt"><span style="line-height:115%"><span b="" nazanin="" style="font-family:"> از جمله </span></span></span><span dir="LTR" style="font-size:12.0pt"><span style="line-height:115%"><span new="" roman="" style="font-family:" times="">miR-155</span></span></span><span lang="AR-SA" style="font-size:12.0pt"><span style="line-height:115%"><span b="" nazanin="" style="font-family:"> و </span></span></span><span dir="LTR" style="font-size:12.0pt"><span style="line-height:115%"><span new="" roman="" style="font-family:" times="">miR-34a</span></span></span><span lang="AR-SA" style="font-size:12.0pt"><span style="line-height:115%"><span b="" nazanin="" style="font-family:"> قادر به هدف‌گیری ژن </span></span></span><span dir="LTR" style="font-size:12.0pt"><span style="line-height:115%"><span new="" roman="" style="font-family:" times="">RAD51</span></span></span><span lang="AR-SA" style="font-size:12.0pt"><span style="line-height:115%"><span b="" nazanin="" style="font-family:"> هستند.</span></span></span></span></span></span></span></span><br> <span style="font-size:11pt"><span style="line-height:115%"><span style="direction:rtl"><span style="unicode-bidi:embed"><span style="font-family:Calibri,sans-serif"><b><span lang="AR-SA" style="font-size:12.0pt"><span style="line-height:115%"><span b="" nazanin="" style="font-family:">&nbsp;نتیجه‌گیری:</span></span></span></b><span lang="AR-SA" style="font-size:12.0pt"><span style="line-height:115%"><span b="" nazanin="" style="font-family:"> یافته‌ها اهمیت تنظیم شبکه‌های ژنی مرتبط با ترمیم </span></span></span><span dir="LTR" style="font-size:12.0pt"><span style="line-height:115%"><span new="" roman="" style="font-family:" times="">DNA</span></span></span><span lang="AR-SA" style="font-size:12.0pt"><span style="line-height:115%"><span b="" nazanin="" style="font-family:"> را در حفظ کیفیت اووسیت نشان داده و بیان می‌کنند که ژن‌های مورد بررسی می‌توانند اهداف بالقوه‌ای برای مداخلات درمانی در ناباروری زنان باشند.</span></span></span></span></span></span></span></span><br> &nbsp;</div> <div style="text-align: justify;"><span style="font-size:11pt"><span style="line-height:107%"><span style="font-family:Calibri,sans-serif"><b><span new="" roman="" style="font-family:" times="">Introduction:</span></b><span new="" roman="" style="font-family:" times=""> Female infertility is a major challenge in reproductive health, influenced by multiple genetic and molecular factors. This study aimed to investigate the role of RAD51 and MRE11 genes in oocyte maturation and their involvement in molecular networks.</span></span></span></span><br> <span style="font-size:11pt"><span style="line-height:107%"><span style="font-family:Calibri,sans-serif"><b><span new="" roman="" style="font-family:" times="">Methods:</span></b><span new="" roman="" style="font-family:" times=""> The protein&ndash;protein interaction network was retrieved from the STRING database and analyzed using Cytoscape. The MCODE algorithm was applied to identify functional clusters, and pathway enrichment tools were used to determine relevant biological pathways. Regulatory miRNAs targeting these genes were examined using the miRTarBase database.</span></span></span></span><br> <span style="font-size:11pt"><span style="line-height:107%"><span style="font-family:Calibri,sans-serif"><b><span new="" roman="" style="font-family:" times="">Results:</span></b><span new="" roman="" style="font-family:" times=""> Network analysis revealed that BRCA1 and BARD1 act as central hub genes, while ATM and ATRX were identified in key functional clusters by MCODE. Enriched pathways indicated the involvement of these genes in homologous recombination, DNA damage response, cellular senescence, and the cell cycle. Furthermore, miRTarBase analysis showed that several miRNAs, including miR-155 and miR-34a, are capable of targeting RAD51 and potentially regulating its expression.</span></span></span></span><br> <span style="font-size:11pt"><span style="line-height:107%"><span style="font-family:Calibri,sans-serif"><b><span new="" roman="" style="font-family:" times="">Conclusion:</span></b><span new="" roman="" style="font-family:" times=""> These findings highlight the critical role of DNA repair&ndash;related gene networks in maintaining oocyte quality and suggest that RAD51, MRE11, and their associated pathways could serve as potential therapeutic targets for female infertility.</span></span></span></span><br> &nbsp;</div> ترمیم DNA, بلوغ اووسیت, RAD51 و MRE11, تحلیل بیوانفورماتیکی DNA repair, oocyte maturation, RAD51 and MRE11, bioinformatics analysis 10223 10234 http://jssu.ssu.ac.ir/browse.php?a_code=A-10-5653-1&slc_lang=fa&sid=1 marjan bababashi مرجان باباباشی marjanbababashi@yahoo.com 0009-0009-0269-154x No Department of Biology, Mashahad Branch, Islamic Azad University, Mashahad, Iran گروه زیست‌شناسی، واحد مشهد، دانشگاه آزاد اسلامی، مشهد، ایران Javad Baharara2 جواد بهار ارا baharara@mshdiau.ac.ir 0000-0001-9728-2945 No Department of Biology, Mashahad Branch, Islamic Azad University, Mashahad, Iran گروه زیست‌شناسی و مرکز تحقیقات زیست‌شناسی کاربردی توسعه حیوانات، واحد مشهد، دانشگاه آزاد اسلامی، مشهد، ایران محمد صالحی Khadije Shahroshabadi1 shahrokhabady@yahoo.com 0000-0002-3536-3456 No Department of Biology, Mashahad Branch, Islamic Azad University, Mashahad, Iran گروه زیست‌شناسی، واحد مشهد، دانشگاه آزاد اسلامی، مشهد، ایران mohammad salehi محمد صالحی msalehi78@gmail.com 0000-0002-3768-4325 Yes Cellular and Molecular Biology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran مرکز تحقیقات زیست‌شناسی سلولی و مولکولی، دانشگاه علوم پزشکی شهید بهشتی، تهران، ایران