Epigenetik Mekanizmalar ve Hepatosellüler Karsinoma

Epigenetik mekanizmalar ökaryotik hücrelerde gen ekspresyonunda ve kromatin organizasyonunda kalıtımsal değişiklikler sağlamaktadır. Epigenetik mekanizmalardaki değişimler; hepatosellüler karsinoma ve diğer birçok hastalıkta önemli rol oynamaktadır. Hepatosellüler karsinoma HCC hem genetik hem de epigenetik bir hastalıktır ve dünya çapında kanser sebepli ölümler arasında üçüncü sıradadır. Hepatokarsinogenez oldukça kompleks ve çok aşamalı bir süreçten oluşmaktadır. Epigenetik değişiklikler, anormal DNA metilasyonu, posttranslasyonel histon modifikasyonları, anormal kodlanmayan RNA miRNA, lnc-RNA gibi ekspresyonu ve kromatinin yeniden modellenmesini içermektedir. Bu mekanizmalar kanser gelişiminde onkogenlerin, tümör baskılayıcı genlerin ve diğer tümörle ilişkili genlerin ekspresyonunu ve yolakların değişimini doğrudan etkilemektedir. Pek çok kompleks miRNA, lnc-RNA uzun kodlanmayan RNA ve piRNA PIWI proteini ile ilişkili RNA regülasyon bozukluğu tümör baskılayıcı genleri hedef alarak dramatik bir şekilde hepatokarsinogeneze dahil olmaktadır. Ayrıca bu genlerin promotör hipermetilasyonu ya da posttranslasyonel regülasyon bozuklukları sebebiyle ekspresyonları azalmaktadır. Hepatokarsinogezde rol alan bu epigenetik mekanizmalar HCC için yeni terapötik yaklaşımlar sunmaktadır. Bu derlemede; hepatosellüler karsinoma oluşumunda etkili epigenetik mekanizmalar konusundaki güncel çalışmaların sonuçları özetlenmiştir.

Anahtar Kelimeler:

Hepatosellüler Karsinoma HCC, epigenetik mekanizmalar, miRNA, lnc-RNA, piRNA

Epigenetic Mechanisms and Hepatocellular Carcinoma

Epigenetic mechanisms provide heritable changes in gene expression and chromatin organization in the eukaryotic cells. Abnormal epigenetic mechanisms particularly play a key role in many different diseases, such as hepatocellular carcinoma. Hepatocellular carcinoma HCC is both genetic and epigenetic disease and is located in the third place in cancer related deaths worldwide. Hepatocarcinogenesis is constituted by a complex, multistep process. Epigenetic changes include aberrant DNA methylation, posttranslational histone modifications, aberrant expression of non-coding RNAs such as miRNAs, lnc-RNAs and chromatin remodeling. These mechanisms can affect directly the expression of oncogenes, tumor suppressor genes and other tumor-related genes and alter the pathways in cancer development. Many complex deregulation of miRNAs, lnc-RNAs long non-coding RNAs and piRNAs PIWI-interacting RNAs are dramatically involved in hepatocarcinogenesis, which target tumor suppressor genes. Furthermore, down-regulation of these genes in HCC is induced by promoter hypermethylation or posttranslational deregulation. The role of these epigenetic mechanisms in hepatocarcinogenesis provide new therapeutic approaches for HCC. In this review, the results of recent studies related with epigenetic mechanisms in the development of hepatocellular carcinoma have been summarized.

Keywords:

Hepatocellular Carcinoma HCC, epigenetic mechanisms, miRNA, lnc-RNA, piRNA,

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