MicroRNAs 146a/b-5 and 425-3p and 24-3p are markers of antidepressant response and regulate MAPK/Wnt-system genes

作者：Juan Pablo López, Laura M. Fiori, Cristiana Cruceanu, Rixing Lin, Benoît Labonté, Hannah M. Cates, Elizabeth A. Heller, Vincent Vialou, Stacy M. Ku, Christophe Gerald, Ming-Hu Han, Jane Allyson Foster, Benicio Noronha Frey, Cláudio N. Soares, Daniel J. Müller, Faranak Farzan, Francesco Leri, GLENDA M. MacQUEEN, Harriet E. Feilotter, Kathrin Tyryshkin, Kenneth Evans, Peter Giacobbe, Pierre Ulrich Blier, Raymond Wing Moon Lam, Roumen V. Milev, Sagar V. Parikh, Susan Rotzinger, Stephen C. Strother, Cathryn M. Lewis, Katherine Jean Aitchison, Gayle M. Wittenberg, Naguib Mechawar, Eric J. Nestler, Rudolf Uher, Sidney H. Kennedy, Gustavo Turecki · 发表于：Nature Communications · 年份：2017 · DOI：10.1038/ncomms15497 · 被引用次数：207 · 研究领域：MicroRNA in disease regulation、Neurogenesis and neuroplasticity mechanisms、RNA Research and Splicing

Antidepressants (ADs) are the most common treatment for major depressive disorder (MDD). However, only ∼30% of patients experience adequate response after a single AD trial, and this variability remains poorly understood. Here, we investigated microRNAs (miRNAs) as biomarkers of AD response using small RNA-sequencing in paired samples from MDD patients enrolled in a large, randomized placebo-controlled trial of duloxetine collected before and 8 weeks after treatment. Our results revealed differential expression of miR-146a-5p, miR-146b-5p, miR-425-3p and miR-24-3p according to treatment response. These results were replicated in two independent clinical trials of MDD, a well-characterized animal model of depression, and post-mortem human brains. Furthermore, using a combination of bioinformatics, mRNA studies and functional in vitro experiments, we showed significant dysregulation of genes involved in MAPK/Wnt signalling pathways. Together, our results indicate that these miRNAs are consistent markers of treatment response and regulators of the MAPK/Wnt systems.