From microRNA target validation to therapy: lessons learned from studies on BDNF.

From microRNA target validation to therapy: lessons learned from studies on BDNF.
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DOI:
10.1007/s00018-015-1836-z
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发表时间:
2015-05
影响因子:
8
通讯作者:
Andressoo, Jaan-Olle
Andressoo, Jaan-Olle
中科院分区:
生物学1区
文献类型:
--
作者:
Varendi, Kart;Matlik, Kert;Andressoo, Jaan-Olle

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在过去的十年中,microRNA(miR)靶标的鉴定已成为常见的实验室实践,并且现在使用各种策略来检测miR及其mRNA靶标之间的相互作用。然而,目前缺乏标准化的身份查验程序往往导致不完整和/或相互矛盾的结果。在这里,我们回顾了验证miR-mRNA相互作用时最常遇到的问题,并提出了未来研究的工作流程。为了说明验证miR靶点时所面临的挑战,我们讨论了miR对脑源性神经营养因子调控的研究,并强调了这些研究中出现的几个争议。最后,我们讨论了miR抑制剂的治疗用途,并讨论了在进行临床前测试之前应该解决的几个问题。
During the past decade, the identification of microRNA (miR) targets has become common laboratory practice, and various strategies are now used to detect interactions between miRs and their mRNA targets. However, the current lack of a standardized identification process often leads to incomplete and/or conflicting results. Here, we review the problems most commonly encountered when verifying miR–mRNA interactions, and we propose a workflow for future studies. To illustrate the challenges faced when validating a miR target, we discuss studies in which the regulation of brain-derived neurotrophic factor by miRs was investigated, and we highlight several controversies that emerged from these studies. Finally, we discuss the therapeutic use of miR inhibitors, and we discuss several questions that should be addressed before proceeding to preclinical testing.
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