De-repressing LncRNA-Targeted Genes to Upregulate Gene Expression: Focus on Small Molecule Therapeutics.
De-repressing LncRNA-Targeted Genes to Upregulate Gene Expression: Focus on Small Molecule Therapeutics.
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DOI：
10.1038/mtna.2014.45
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发表时间：
2014-11-18
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非蛋白质编码RNA(NcRNAs)构成了基因组中绝大多数的转录本，最近因其在细胞中的复杂调控作用而受到关注，包括对蛋白质编码基因的调控。此外，ncRNAs在正常发育过程中发挥着重要作用，在一些疾病中其表达水平受到失调。近年来，一些长的非编码RNA(LncRNAs)被证明可以改变基因组座位的表观遗传状态，抑制靶基因的表达。这篇综述将提供这种机制的例子，并重点关注靶向lncRNAs通过抑制在各种疾病中表观遗传沉默的基因来实现治疗性基因上调的可能性。最后，将讨论通过与表观遗传酶相互作用，使用小分子、病毒载体和反义寡核苷酸等各种工具来靶向lncRNAs的可能性。我们认为，一类新的药物靶点的小分子调节剂，即lncRNA-蛋白质相互作用，在治疗某些癌症、心血管疾病和神经疾病方面具有巨大的潜力。
Non-protein coding RNAs (ncRNAs) make up the overwhelming majority of transcripts in the genome and have recently gained attention for their complex regulatory role in cells, including the regulation of protein-coding genes. Furthermore, ncRNAs play an important role in normal development and their expression levels are dysregulated in several diseases. Recently, several long noncoding RNAs (lncRNAs) have been shown to alter the epigenetic status of genomic loci and suppress the expression of target genes. This review will present examples of such a mechanism and focus on the potential to target lncRNAs for achieving therapeutic gene upregulation by de-repressing genes that are epigenetically silenced in various diseases. Finally, the potential to target lncRNAs, through their interactions with epigenetic enzymes, using various tools, such as small molecules, viral vectors and antisense oligonucleotides, will be discussed. We suggest that small molecule modulators of a novel class of drug targets, lncRNA-protein interactions, have great potential to treat some cancers, cardiovascular disease, and neurological disorders.
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