caa a22 4500 606175296 CHVBK 20210128100742.0 cr unu---uuuuu 210128e20150501xx s 000 0 eng 10.1007/s00018-015-1836-z doi (NATIONALLICENCE)springer-10.1007/s00018-015-1836-z From microRNA target validation to therapy: lessons learned from studies on BDNF [Elektronische Daten] [Kärt Varendi, Kert Mätlik, Jaan-Olle Andressoo] 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. The Author(s), 2015 microRNA nationallicence 3′UTR nationallicence RNA secondary structure nationallicence Luciferase assay nationallicence AntagomiRs nationallicence BDNF nationallicence AD : Alzheimer's disease nationallicence AM : AntagomiR nationallicence ARPE-19 : Human artificial retinal pigment epithelial cells nationallicence bEnd.3 : Immortalized mouse brain endothelial cell line nationallicence BDNF : Brain-derived neurotrophic factor nationallicence C2C12 : Mouse myoblast cell line nationallicence ChIP-seq : Chromatin immunoprecipitation combined with massively parallel DNA sequencing nationallicence H9c2 : Rat cardiac myoblast cell line nationallicence HEK-293 : Human embryonic kidney cell line nationallicence HeLa : Human cervical cancer cell line nationallicence HUVEC : Human umbilical vein endothelial cells nationallicence LNA : Locked nucleic acid nationallicence MCF7 : Michigan Cancer Foundation-7 human breast cancer cell line nationallicence miR : MicroRNA nationallicence MRE : MicroRNA response element nationallicence Neuro2a : Mouse neuroblastoma cell line nationallicence NG108-15 : Hybrid cell line from fused mouse neuroblastoma and rat glioblastoma cells nationallicence SCG7901 : Human gastric cancer cell line nationallicence SH-SY5Y : Human neuroblastoma cell line nationallicence U-87 MG : Human glioblastoma cell line nationallicence UTR : Untranslated region nationallicence Varendi Kärt Institute of Biotechnology, University of Helsinki, 00014, Helsinki, Finland aut Mätlik Kert Institute of Biotechnology, University of Helsinki, 00014, Helsinki, Finland aut Andressoo Jaan-Olle Institute of Biotechnology, University of Helsinki, 00014, Helsinki, Finland aut Cellular and Molecular Life Sciences Springer Basel 72/9(2015-05-01), 1779-1794 1420-682X 72:9<1779 2015 72 18 https://doi.org/10.1007/s00018-015-1836-z text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 review-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00018-015-1836-z text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Varendi Kärt Institute of Biotechnology, University of Helsinki, 00014, Helsinki, Finland aut NATIONALLICENCE 700 1- Mätlik Kert Institute of Biotechnology, University of Helsinki, 00014, Helsinki, Finland aut NATIONALLICENCE 700 1- Andressoo Jaan-Olle Institute of Biotechnology, University of Helsinki, 00014, Helsinki, Finland aut NATIONALLICENCE 773 0- Cellular and Molecular Life Sciences Springer Basel 72/9(2015-05-01), 1779-1794 1420-682X 72:9<1779 2015 72 18