Neurogenetics Unit, 1st Department of Neurology, University of Athens Medical School, Eginition Hospital, Athens, Greece.
Curr Top Med Chem. 2013;13(13):1573-88. doi: 10.2174/15680266113139990106.
MicroRNAs (miRNAs) are small non-coding RNAs approximately 22 nucleotides in length that play a pivotal role in post-transcriptional gene regulation by binding to complementary sites in the 3'-untranslated region of messenger RNAs. In the past decade, their role in several human diseases, from cancer to cardiovascular disease, has been established by a wealth of evidence. Stroke is responsible for 10% of deaths worldwide and is one of the leading causes of disability. MiRNAs are involved in stroke risk factors including hypertension, atherosclerosis, atrial fibrillation, diabetes and dyslipidemia. The role of miRNAs in the pathophysiology of stroke has been the subject of more recent investigations. Animal studies, which dominate the field, have demonstrated the differential expression of miRNAs in brain and blood following ischemic or hemorrhagic insult and the potential use of miRNA antagonists to reduce focal cerebral damage. In particular, antagomirs to miR-145, -497, -181a, -1 and let-7f have been found to be neuroprotective in vivo. The discovery of circulating miRNAs in peripheral blood, which are unexpectedly stable, has allowed the recent completion of several studies in human stroke patients that have confirmed the differential expression of specific miRNAs following stroke and have addressed their potential use as diagnostic and prognostic markers. With miRNA research in stroke still in its infancy, it is anticipated that in the next few years significant discoveries that may have important therapeutic implications will emerge.
微小 RNA(miRNA)是大约 22 个核苷酸长的小非编码 RNA,通过与信使 RNA 的 3'非翻译区中的互补位点结合,在转录后基因调控中发挥关键作用。在过去的十年中,大量证据表明 miRNA 在从癌症到心血管疾病等多种人类疾病中发挥作用。中风占全球死亡人数的 10%,是导致残疾的主要原因之一。miRNA 参与中风的危险因素,包括高血压、动脉粥样硬化、心房颤动、糖尿病和血脂异常。miRNA 在中风病理生理学中的作用是最近研究的主题。动物研究主导着这一领域,已经证明了缺血性或出血性损伤后大脑和血液中 miRNA 的差异表达,以及使用 miRNA 拮抗剂减少局灶性脑损伤的潜力。特别是,miR-145、-497、-181a、-1 和 let-7f 的拮抗剂在体内具有神经保护作用。在外周血中发现循环 miRNA 出人意料地稳定,这使得最近能够在人类中风患者中完成几项研究,这些研究证实了中风后特定 miRNA 的差异表达,并探讨了它们作为诊断和预后标志物的潜在用途。由于中风的 miRNA 研究仍处于起步阶段,预计在未来几年内可能会有重要的治疗意义的发现出现。