miRNAs in Health and Disease

Abstract

microRNAs (miRNAs) are small, non-coding RNA molecules (~19–24 nucleotides) that post-transcriptionally regulate gene expression by inducing mRNA degradation or translational repression. Since the discovery of lin-4 in 1993, a milestone honored with the 2024 Nobel Prize, miRNAs have been estimated to regulate over 60% of human protein-coding genes. This review examines the canonical and non-canonical biogenesis pathways of miRNAs, emphasizing their role as homeostatic rheostats across major physiological systems, including embryogenesis, immunity, metabolism, neurobiology, and cardiovascular function. Dysregulation of these evolutionarily conserved regulatory networks contributes to the pathogenesis of human disorders, notably cancer, neurodegeneration, metabolic disorders, and autoimmune conditions. Given their stability in biofluids, circulating miRNAs have potential as diagnostic and prognostic biomarkers; however, most candidate signatures remain investigational and require prospective clinical validation. Therapeutic strategies based on miRNA mimics and inhibitors have reached preclinical and early-phase clinical testing, with outcomes ranging from completed proof-of-concept studies to terminated trials. Advances in nanotechnology, high-throughput sequencing, CRISPR-based tools, and precision medicine support the development of miRNA-based diagnostics and therapeutics, but routine clinical use still depends on standardized assays, reliable delivery, and evidence of safety and clinical benefit in the relevant biological context.

Keywords

• mİRNAs
• post-transcriptional gene regulation
• circulating biomarkers
• oncomiRs
• RNA therapeutics

Supporting Institution

Nevşehir Hacı Bektaş Veli University

Ethical Statement

Ethics committee approval is not required for this review article.

Thanks

The author would like to thank Professor Hikmet Geçkil (Department of Molecular Biology and Genetics, Inonu University) for critically reading the manuscript and providing valuable suggestions that improved the final version of this review.

Sağlık ve Hastalıkta miRNA'lar

Abstract

mikroRNA'lar (miRNA'lar), mRNA bozunmasını veya translasyonel baskılamayı indükleyerek gen ekspresyonunu transkripsiyon sonrası düzenleyen küçük, kodlayıcı olmayan RNA molekülleridir (~19-24 nükleotid). 1993 yılında lin-4'ün keşfinden (2024 Nobel Ödülü ile onurlandırılan bir dönüm noktası) bu yana, miRNA'lar insan protein kodlayan genlerinin %60'ından fazlasını düzenlediği tahmin edilen transkripsiyon sonrası düzenleyiciler olarak ortaya çıkmıştır. Bu derleme, miRNA'ların kanonik ve kanonik olmayan biyogenez yollarını inceler ve embriyogenez, bağışıklık, metabolizma, nörobiyoloji ve kardiyovasküler fonksiyon dahil olmak üzere başlıca fizyolojik sistemlerde homeostatik düzenleyiciler olarak rollerini vurgular. Evrimsel olarak korunmuş bu düzenleyici ağların düzensizliği, başta kanser, nörodejenerasyon, metabolik hastalıklar ve otoimmün durumlar olmak üzere çeşitli insan hastalıklarının patogenezine katkıda bulunur. Biyolojik sıvılardaki kararlılıkları nedeniyle dolaşımdaki miRNA'lar, tanısal ve prognostik biyobelirteçler olarak potansiyel taşımaktadır; ancak aday imzaların çoğu hâlen araştırma aşamasındadır ve prospektif klinik doğrulama gerektirir. miRNA taklitleri ve inhibitörlerine dayalı terapötik stratejiler preklinik ve erken faz klinik değerlendirmeye ulaşmış olup, çalışmaların sonuçları tamamlanmış kavram kanıtlama çalışmalarından sonlandırılmış çalışmalara kadar değişmektedir. Nanoteknoloji, yüksek verimli dizileme, CRISPR tabanlı araçlar ve hassas tıp alanlarındaki gelişmeler miRNA temelli tanı ve tedavilerin geliştirilmesini desteklese de rutin klinik kullanım için standartlaştırılmış testlere, güvenilir taşıma yöntemlerine ve ilgili biyolojik bağlamda güvenlik ile klinik yararı gösteren kanıtlara ihtiyaç vardır.

Keywords

• miRNA’lar
• transkripsiyon sonrası gen düzenlemesi
• dolaşımdaki biyobelirteçler
• onkomiR’ler
• RNA terapötikleri

Supporting Institution

Nevşehir Hacı Bektaş Veli Üniversitesi

Ethical Statement

Bu inceleme makalesi için etik kurul onayı gerekmemektedir.

Thanks

Yazar, makaleyi eleştirel bir şekilde okuyup son halini geliştiren değerli önerilerde bulunan İnönü Üniversitesi Moleküler Biyoloji ve Genetik Bölümü'nden Profesör Hikmet Geçkil'e teşekkür etmek ister.

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