Beyin-Kalp Ekseni Üzerine Bilgisayar Tabanlı Bir Çalışma: Kalp Yetmezliğinde miR-423-5p

Öz

Kalp yetmezliği (KY), yüksek mortalite ve morbidite oranlarına sahip çoklu organ ve sistemleri etkileyen kompleks bir klinik sendromdur. Son yıllarda kalp ve beyin arasındaki çift yönlü iletişimi tanımlayan kalp-beyin ekseni (KBA), KY’nin patofizyolojisinin anlaşılmasında önemli bir kavram olarak öne çıkmıştır. Bu eksen kapsamında dolaşımdaki mikroRNA’ların (miRNA), organlar arası moleküler sinyal iletiminde rol oynayabileceği düşünülmektedir. Bu çalışmanın amacı, KY’de değiştiği bildirilen miRNA’lar arasından miR-423-5p’yi odak miRNA olarak belirlenmesi, KBA ile ilişkili olası moleküler mekanizmaları bilgisayar tabanlı yöntemlerle araştırmayı amaçlamıştır. Bu amaç doğrultusunda insan kan, serum veya plazma örneklerinden elde edilen literatür verileri dahil edilme kriterleri göz önüne alınarak incelenmiş elde edilen miRNA'lar ortaya koyulmuştur. Bu miRNA'ların beyinde ekspresyonları ve bağımsız çalışmada tutarlı biçimde değişimi incelenmiştir. Bu doğrultuda miR-423-5p potensiyel aday olarak belirlenmişr ve miR-423-5p’nin hedef genleri miRDB, TargetScan, miRWalk ve DIANA-microT veritabanları kullanılarak tahmin edilmiştir. Bu dört databasde -ortak olarak yer alan 75 yüksek güvenilir hedef gen analize dahil edilerek fonksiyonel zenginleştirme ve protein–protein etkileşim analizleri Metascape platformu aracılığıyla gerçekleştirilmiştir. Analiz sonuçları, miR-423-5p hedef genlerinin hücre içi sinyal iletimi, protein fosforilasyonu ve nöronal süreçlerle ilişkili biyolojik yolaklarda yoğunlaştığını göstermiştir. Ayrıca PRKACA, bu ağın merkezinde yer alan başlıca hub protein olarak tanımlanmıştır. Sonuç olarak bu çalışma, miR-423-5p’nin HF'de BKA ile ilişkili moleküler ağlarda potansiyel bir düzenleyici rol oynayabileceğini göstermek olup ve gelecekte yapılacak deneysel çalışmalar için hipotez oluşturucu bir temel sunmaktadır.

Anahtar Kelimeler

• kalp yetmezliği
• miRNA
• beyin

A Computer-Based Study on Brain-Heart Axis: miR-423-5p in Heart Failure

Öz

A Computer-Based Study on Brain-Heart Axis: miR-423-5p in Heart Failure Heart failure (HF) is a complex clinical syndrome affecting multiple organs and systems with high mortality and morbidity rates. In recent years, the heart-brain axis (HBA), that describes the bidirectional communication between the heart and brain, has emerged as a crucial concept in understanding the pathophysiology of HF. Within the axis, circulating microRNAs (miRNAs) are thought to play a role in inter-organ molecular signaling. The aim of this study was to identify miR-423-5p as a focal miRNA among those reported to be altered in HF and to investigate possible molecular mechanisms associated with HBA in silico approches. For the aim, literature data obtained from human blood, serum, or plasma samples were examined, considering the inclusion criteria, and the identified miRNAs were determined. The expression of these miRNAs in the brain and their consistent alteration in independent studies were investigated. Accordingly, miR-423-5p was recognized as a potential candidate, and its target genes were predicted using the miRDB, TargetScan, miRWalk, and DIANA-microT databases. Total of 75 highly reliable target genes from these four databases were included in the analysis, and functional enrichment and protein-protein interaction analyses were performed via the Metascape platform. The analysis results showed that miR-423-5p target genes are concentrated in biological pathways related to intracellular signal transduction, protein phosphorylation, and neuronal processes. Moreover, PRKACA was identified as the main hub protein at the center of the network. In conclusion, this study demonstrates that miR-423-5p may play a potential regulatory role in HBA-related molecular networks in HF and provides a hypothesis-forming basis for future experimental studies.

Anahtar Kelimeler

• Heart Failure
• miRNA
• Brain

Kaynakça

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