MikroRNA'lar; küçük, kodlamayan RNA'lar olup, hedef mRNA'lara bağlanıp bozulmalarını indükleyerek veya translasyonlarını inhibe ederek gen ekspresyonunu düzenlemektedirler. Her bir mikroRNA'nın yüzlerce hedefi olabilmekte, bu nedenle mikroRNA'lar genlerin büyük bir kısmının ekspresyonunu etkilemektedir. Yaklaşık 20 yıl önce memeli hücrelerinde keşfedilmelerinden beri, insan sağlığında ve hastalıklarında mikroRNA'ların rolü araştırılmaktadır. Yakın zamanda yapılan çalışmalar, mikroRNA'ların kalıtsal ve adaptif immün sistem hücrelerinde benzersiz bir ekspresyon profili ile bu hücrelerin gelişmesi ve fonksiyonlarında çok önemli rolleri olduğunu göstermiştir. miR-146 (146a ve 146b) ve miR-155, kalıtsal ve adaptif immün sistemin kontrolündeki çoklu rolleri ve bazı tümörlerdeki düzenleyici ve onkogenik rolleri nedeni ile, bu konuda en fazla araştırılan mikroRNA'lardır. İmmün sistemin uygun yanıtının organizasyonundaki hayati rollerinin dışında, mikroRNA'lar ayrıca, hücre içi immün mediyatör olarak görev almaktadırlar. Bu şekilde viral RNA'yı tanıyıp, viral RNA'nın stabilitesini ve translasyonunu negatif yönde düzenleyebilmektedirler. Dahası, mikroRNA'ların anormal ekspresyonu, immün sistem ile ilgili kanser ve otoimmün hastalıklar gibi patolojik durumların ortaya çıkmasında da rol oynayabilmektedir. Bu mikroRNA'ların çoğu, birçok hastalıkta biyogösterge olarak veya terapötik seçenek olarak incelenmektedir. Birçok vakada, mikroRNA ekpresyon paneli kanserin klinik ve/veya patolojik parametreleri ile ilişkili bulunmuştur. Bu çalışmada, mikroRNA'ların immün sistemin gelişmesindeki fonksiyonları hakkında genel bir değerlendirme sunulması, ayrıca, mikroRNA'ların anormal ekspresyonlarının patolojik rolü ve mikroRNA temelli terapötik yaklaşımların da vurgulanması amaçlanmıştır.
Anahtar Kelimeler: mikroRNAlar; bağışıklık sistemi
MicroRNAs are small noncoding RNAs that regulate gene expression by binding to target mRNAs and either promoting their decay or inhibiting their translation. Each microRNAs can have hundreds of targets; therefore, microRNAs influence the expression of a large proportion of genes. The functions of microRNAs in human health and diseases have been investigated since their discovery in mammalian cells approximately twelve years ago. Recent studies have shown that microRNAs have unique expression profiles in cells of the innate and adaptive immune systems and have pivotal roles in the regulation of both cell development and function. miR-146 (146a and 146b) and miR-155 are among the most studied microRNAs for their multiple roles in the control of the innate and adaptive immune processes and for their regulative and oncogenic role in some tumors. In addition to the vital role of miRNA in co-ordinating the appropriate behaviour of the immune system, miRNA is also capable of acting as an intracellular immune mediator. In this way, microRNAs can recognize viral RNA and down-modulate viral RNA stability and translation. Furthermore, when microRNAs are aberrantly expressed they can contribute to pathological conditions involving the immune system, such as cancer and autoimmunity. Many of these microRNAs are currently under investigation as biomarkers or therapeutic options in a range of diseases. In many cases, miRNA expression patterns have been correlated with clinical and/or pathological parameters of the cancer. The purpose of this review is to provide an overview of the functions of microRNAs involved in the development of the immune system. In addition, their pathological roles when their expression is dysregulated and developments of miRNA-based therapeutics will be highlighted.
Keywords: microRNAs; immune system
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