نام و نام خانوادگی:راضیه فتحی
عنوان پایان نامه: بررسی بیوانفورماتیکی و بیانی ریبونوکلئیک اسیدهای بلند غیر کد شونده MIR4435-2HG و TTC28-AS1 در سلول های گرانولوزا بیماران مبتلا به PCOS و افراد نرمال
رشته تحصیلی: زيست فناوري – ميکروبی
مقطع تحصیلی: کارشناسی ارشد ناپیوسته
استاد راهنما : دکتر محمدحسین نصر اصفهانی
چکیده:
Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women of reproductive age, characterized by ovulation disorder, hyperandrogenism, polycystic ovary morphology and genetic heterogeneity. Despite the extensive research that has been done on this disease, its main cause or causes are still unknown. It is now well accepted that altered activities of long non-coding RNAs (lncRNAs) are associated with the development of human diseases. However, the role of lncRNAs is unknown in reproductive medicine, except for limited cases that include the effect of changing the expression of lncRNAs on the proliferation and steroidogenesis of granulosa cells in women with PCOS.
Here, we aim to identify key lncRNAs involved in the development or exacerbation of PCOS using bioinformatics studies. Two microarray datasets were extracted from the GEO gene expression database. Among them, genes with different and significant expression (DEGs) were identified. Then, two key lncRNAs, TTC28-AS1 and MIR4435-2HG, were selected from the lncRNA list based on their correlation with each other and with the genes identified in the previous step. The measurement of the expression of these two lncRNAs was consistent with the analyzes performed in such a way that TTC28-AS1 lncRNA showed a significant decrease in expression in the PCOS group compared to the control group, and MIR4435-2HG lncRNA showed an increase in expression that was expected, but this The change was not significant. Then the relationship between the expression of TTC28-AS1 lncRNA and the clinical, biochemical and hormonal parameters of both groups in the study was investigated. The results showed a significant correlation between TTC28-AS1 lncRNA expression and LH, FSH, AMH and testosterone levels. The oocyte/embryo quality in PCOS patients undergoing ART cycles was evaluated and its relationship with TTC28-AS1 expression was investigated. Among these data, only the percentage of germinal vesicles, degenerated oocytes and the number of embryos had a significant correlation with the expression of TTC28-AS1.
The genes regulated by two candidate lncRNAs were also identified, which included FOS, PFKFB4, EGR2, TBC1D22A, ARHGEF40, and ENO2, and it was shown that they are active in various pathways such as TNF-alpha, cholesterol homeostasis, hypoxia, p53 pathway, and apoptosis. do Since it is possible that the differential expression analysis of lncRNAs can introduce diagnostic biomarkers for therapeutic purposes and suggest new approaches to understand the pathogenesis of this syndrome. In this study, the above genes are suggested as potential biomarkers for PCOS diagnosis in peripheral blood. Finally, using drug databases such as TTD، DGIdb، GeneCards, possible drugs (metformin, pioglitazone, dexamethazone, propofol and Capsaicin) that can regulate the obtained candidate genes were proposed and reported.
کلیدواژه: polycystic ovary syndrome, PCOS, lncRNAs, TTC28-AS1, infertility