Didem Turgut COŞAN, EMİNE YAĞCI, Hülyam KURT

Epigenetikten Kansere Uzanan Çizgiler: Uzun Kodlamayan RNA’lar

İnsan genomununda protein kodlama kapasitesine sahip olmayan transkriptler kodlamayan RNA (ncRNA) olarak adlandırılmaktadır. Bu kodlamayan RNA’lar uzunluklarına göre küçük kodlamayan RNA’lar (sncRNA) ve uzun kodlamayan RNA'lar (lncRNA) olarak iki ana kategoriye ayrılır. LncRNA'lar, >200 nükleotidden oluşan bir grup kodlamayan RNA'dır. Gen ekspresyonunun cis ve trans regülasyonu, çekirdeğin epigenetik modülasyonu ve sitoplazmada post-transkripsiyonel kontrolü de içeren moleküler ve biyokimyasal mekanizmalar yoluyla işlev görürler. LncRNA’lar hücrede sitoplazma, çekirdek ve mitokondri gibi alanlara lokalize olabilirler ve lokalize oldukları yere göre fonksiyonları değişiklik gösterebilir. Kromatin durumunu modüle etmek için çeşitli kromatin remodelingte rol oynayan komplekslerle etkileşme kapasitesine sahiptirler. LncRNA'ların bu kabiliyeti, epigenetik yapıyı değiştirerek gen ekspresyonunu kontrol edebilir. Son yıllarda yapılan çalışmalar, lncRNA'ların onkojenik veya tümör baskılayıcı fonksiyonu olabileceğini göstermektedir; bu da onların kanser gelişiminde ve ilerlemesinde önemli bir rol oynadığını ortaya koymaktadır. LncRNA'lar birçok kanser türünde önemli rol oynar. Nüks ve prognozu öngörmek için biyolojik belirteç olarak kullanılabileceklerinden dolayı kanserde potansiyel terapötik hedefler olarak gösterebilirler. Bu derlemede, lncRNA'ların genel özellikleri, lokalizasyonları, fonksiyonları ve kanser ile ilişkili olan lncRNA çeşitlerine değinilecektir. Böylece okuyucularda, gelecekte çeşitli kanserlerin progresyonunda önemli ara bileşenler olabileceği düşünülen lncRNA’larla, henüz tam olarak açıklığa kavuşmamış bazı kanser mekanizmaları arasındaki ilişki hakkında farklı bakış açılarının oluşturulması amaçlanmaktadır.

Anahtar Kelimeler:

Uzun kodlamayan RNA’lar, gen ekspresyonu, kanser, epigenetik

Extending Lines from Epigenetic to Cancer: Long Non-coding RNAs

Transcripts that do not have the protein coding capacity in the human genome are called non- coding RNAs (ncRNAs). These non-coding RNAs are divided into two major categories as small non-coding RNAs (sncRNA) and long non-coding RNAs (lncRNA), depending on their length. LncRNAs are a group of non-coding RNAs of > 200 nucleotides. They function through molecular and biochemical mechanisms, including cis and trans regulation of gene expression, epigenetic modulation of the nucleus and post-transcriptional control in the cytoplasm. LncRNAs may localize to part such as cytoplasm, nucleus, and mitochondria in the cell, and may alter their function depending on where they are localized. They have the ability to interact with various chromatin modifying complexes to modulate the chromatin state. The ability of collect and bind to chromatin to these complexes of lncRNAs can control gene expression by altering epigenetic structure. Recent studies have shown that lncRNAs may be an oncogenic or tumor suppressor function; suggesting that lncRNAs play an important role in the development and progression of cancer. LncRNAs play an important role in many types of cancer, and they may represent potential therapeutic targets because they can be used as biomarkers to predict recurrence and prognosis. In this review, will refer to the general characteristics, localizations, functions of lncRNAs, and cancer-related lncRNAs. Thus, it is intended that readers will have different views on the relationship between lncRNAs, which are thought to be important intermediates in the progression of various cancers in the future, and some cancer mechanisms that have not yet been fully exploited.

Keywords:

Long non-coding RNAs, gene expression, cancer, epigenetic,

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