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From microRNA target validation to therapy: lessons learned from studies on BDNF
- Varendi, Kärt, Mätlik, Kert, Andressoo, Jaan-Olle
- Cellular and molecular life sciences 2015 v.72 no.9 pp. 1779-1794
- messenger RNA, microRNA, therapeutics
- 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.