Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California, USA.
Mol Ther Nucleic Acids. 2013 Jul 9;2(7):e104. doi: 10.1038/mtna.2013.33.
Small noncoding antisense RNAs (sasRNAs) guide epigenetic silencing complexes to target loci in human cells and modulate gene transcription. When these targeted loci are situated within a promoter, long-term, stable epigenetic silencing of transcription can occur. Recent studies suggest that there exists an endogenous form of such epigenetic regulation in human cells involving long noncoding RNAs. In this article, we present and validate an algorithm for the generation of highly effective sasRNAs that can mimic the endogenous noncoding RNAs involved in the epigenetic regulation of gene expression. We validate this algorithm by targeting several oncogenes including AKT-1, c-MYC, K-RAS, and H-RAS. We also target a long antisense RNA that mediates the epigenetic repression of the tumor suppressor gene DUSP6, silenced in pancreatic cancer. An algorithm that can efficiently design small noncoding RNAs for the epigenetic transcriptional silencing or activation of specific genes has potential therapeutic and experimental applications.Molecular Therapy-Nucleic Acids (2013) 2, e104; doi:10.1038/mtna.2013.33; published online 9 July 2013.
小非编码反义 RNA（sasRNA）引导表观遗传沉默复合物靶向人细胞中的靶位，并调节基因转录。当这些靶向位点位于启动子时，转录的长期、稳定的表观遗传沉默就会发生。最近的研究表明，人类细胞中存在一种涉及长非编码 RNA 的内源性表观遗传调控形式。在本文中，我们提出并验证了一种生成高效 sasRNA 的算法，该算法可以模拟参与基因表达表观遗传调控的内源性非编码 RNA。我们通过靶向包括 AKT-1、c-MYC、K-RAS 和 H-RAS 在内的几个癌基因来验证该算法。我们还靶向一种长反义 RNA，该 RNA 介导肿瘤抑制基因 DUSP6 的表观遗传抑制，该基因在胰腺癌中沉默。一种能够有效设计用于特定基因的表观遗传转录沉默或激活的小非编码 RNA 的算法具有潜在的治疗和实验应用。《分子治疗-核酸》（2013）2，e104；doi:10.1038/mtna.2013.33；在线发表于 2013 年 7 月 9 日。
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