AİLEVİ AKDENİZ ATEŞİ İLE İLİŞKİLİ miR-197-3p’NİN İFADESİNİ DÜZENLEYEN UZUN KODLAMAYAN RNA’LARIN ARAŞTIRILMASI

Abstract

Familial Mediterranean Fever (FMF) is a monogenic autoinflammatory disease characterized by dysregulated activation of innate immune responses. Excessive activation of the interleukin-1 beta (IL-1β) signaling pathway plays a central role in FMF pathogenesis, and the contribution of epigenetic regulators to this process has gained increasing attention. In recent years, microRNAs (miRNAs) have been shown to modulate inflammatory responses, and particularly miR-197-3p has been reported to be downregulated in FMF patients, exerting anti-inflammatory effects through its target, interleukin-1 receptor type 1 (IL1R1). However, the regulatory mechanisms underlying the decreased levels of miR-197-3p have not been fully elucidated. In this thesis, long non-coding RNAs (lncRNAs) with the potential to regulate miR-197-3p expression were identified, and the effects of these lncRNAs on the miR-197-3p–IL1R1 regulatory axis were investigated. Candidate lncRNAs were screened using multiple databases and further intersected with RNA-sequencing data. The intracellular expression levels of selected lncRNAs were experimentally modulated, and the resulting changes in miR-197-3p and IL1R1 expression were analyzed. Based on the results of the analyses, overexpression of LINC00641 and MCM3AP-AS1 was found to reduce miR-197-3p levels (p = 0.0138 and p = 0.0253, respectively), whereas suppression of MCM3AP-AS1 led to a 25.82-fold increase in miR-197-3p expression (p = 0.0005). In addition, suppression of these lncRNAs resulted in decreased IL1R1 mRNA levels, while only overexpression of MCM3AP-AS1 increased IL1R1 expression. These findings suggest that MCM3AP-AS1 may act as an important epigenetic regulator within the miR-197-3p–IL1R1 regulatory axis in AAA. Overall, this study indicates that MCM3AP-AS1 may contribute to AAA-associated inflammatory processes through the miR-197-3p–IL1R1 axis and highlights this lncRNA as a potential biomarker or therapeutic target.