The Promise and Challenge of Therapeutic MicroRNA Silencing in Diabetes and Metabolic Diseases.
The Promise and Challenge of Therapeutic MicroRNA Silencing in Diabetes and Metabolic Diseases.
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DOI：
10.1007/s11892-016-0745-3
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发表时间：
2016-06
影响因子：
4.2
通讯作者：
Sethupathy P
中科院分区：
文献类型：
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作者：
Sethupathy P
MicroRNA (miRNA) 是调节基因表达的小型非编码 RNA 分子。它们具有悠久的进化历史，存在于植物、病毒和动物中。尽管最初于 1993 年在秀丽隐杆线虫中发现，但直到 2000 年代初期，它们才被认为是广泛且丰富的基因调节因子。过去十年的研究发现，miRNA 在面对环境扰动时具有表型鲁棒性，可以作为疾病的诊断和预后指标，是多种复杂疾病的病理学基础，并代表引人注目的治疗靶点。动物模型的临床前研究表明，对 miRNA（主要是在肝脏中）的药理学操作可以调节代谢表型，甚至逆转胰岛素抵抗和糖尿病的进程。该领域对基于 miRNA 的糖尿病疗法持谨慎乐观态度，其中一些疗法已经处于不同的临床试验阶段。这篇综述将强调治疗性 miRNA 沉默在糖尿病及相关疾病中的前景和最紧迫的挑战。
MicroRNAs (miRNAs) are small, non-coding, RNA molecules that regulate gene expression. They have a long evolutionary history and are found in plants, viruses, and animals. Although initially discovered in 1993 in Caenorhabditis elegans, they were not appreciated as widespread and abundant gene regulators until the early 2000s. Studies in the last decade have found that miRNAs confer phenotypic robustness in the face of environmental perturbation, may serve as diagnostic and prognostic indicators of disease, underlie the pathobiology of a wide array of complex disorders, and represent compelling therapeutic targets. Pre-clinical studies in animal models have demonstrated that pharmacologic manipulation of miRNAs, mostly in the liver, can modulate metabolic phenotypes and even reverse the course of insulin resistance and diabetes. There is cautious optimism in the field about miRNA-based therapies for diabetes, several of which are already in various stages of clinical trials. This review will highlight both the promise and the most pressing challenges of therapeutic miRNA silencing in diabetes and related conditions.