Targeting noncoding RNAs in disease
Brian D. Adams, … , Wen Cai Zhang, Frank J. Slack
Brian D. Adams, … , Wen Cai Zhang, Frank J. Slack
Published March 1, 2017
Citation Information: J Clin Invest. 2017;127(3):761-771. https://doi.org/10.1172/JCI84424.
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Category: Review

Targeting noncoding RNAs in disease

Abstract

Many RNA species have been identified as important players in the development of chronic diseases, including cancer. Over the past decade, numerous studies have highlighted how regulatory RNAs such as microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) play crucial roles in the development of a disease state. It is clear that the aberrant expression of miRNAs promotes tumor initiation and progression, is linked with cardiac dysfunction, allows for the improper physiological response in maintaining glucose and insulin levels, and can prevent the appropriate integration of neuronal networks, resulting in neurodegenerative disorders. Because of this, there has been a major effort to therapeutically target these noncoding RNAs. In just the past 5 years, over 100 antisense oligonucleotide–based therapies have been tested in phase I clinical trials, a quarter of which have reached phase II/III. Most notable are fomivirsen and mipomersen, which have received FDA approval to treat cytomegalovirus retinitis and high blood cholesterol, respectively. The continued improvement of innovative RNA modifications and delivery entities, such as nanoparticles, will aid in the development of future RNA-based therapeutics for a broader range of chronic diseases. Here we summarize the latest promises and challenges of targeting noncoding RNAs in disease.

Authors

Brian D. Adams, Christine Parsons, Lisa Walker, Wen Cai Zhang, Frank J. Slack

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Figure 1

The complexity of noncoding RNA gene networks.

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The complexity of noncoding RNA gene networks. In this scenario, four ge...
In this scenario, four genes are transcribed. However, only the splice variants mRNA-1 and mRNA-2 encoded by gene A are translated into protein products. These protein products can be regulated by noncoding RNAs (ncRNAs) that are encoded by genes B, C, and D, which interact with gene A at the RNA level in what is referred to as an RNA language or RNA network. Gene B encodes miRNA, which can interact with mRNAs at their 3′-UTR. Gene C encodes long noncoding RNA (lncRNA), which can interact with the protein products of gene A or serve as a decoy for certain miRNAs. Gene D encodes circular RNA (circRNA), which can sponge or serve as a decoy for any RNA binding event that indirectly regulates gene A protein products, such as lncRNA or miRNA interactions.