Dysregulation of miRNA-9 in a Subset of Schizophrenia Patient-Derived Neural Progenitor Cells.

["Topol, Aaron", "Zhu, Shijia", "Hartley, Brigham J", "English, Jane", "Hauberg, Mads E", "Tran, Ngoc", "Rittenhouse, Chelsea Ann", "Simone, Anthony", "Ruderfer, Douglas M", "Johnson, Jessica", "Readhead, Ben", "Hadas, Yoav", "Gochman, Peter A", "Wang, Ying-Chih", "Shah, Hardik", "Cagney, Gerard", "Rapoport, Judith", "Gage, Fred H", "Dudley, Joel T", "Sklar, Pamela", "Mattheisen, Manuel", "Cotter, David", "Fang, Gang", "Brennand, Kristen J"]

Cell reports 2016

Open on PubMed

Converging evidence indicates that microRNAs (miRNAs) may contribute to disease risk for schizophrenia (SZ). We show that microRNA-9 (miR-9) is abundantly expressed in control neural progenitor cells (NPCs) but also significantly downregulated in a subset of SZ NPCs. We observed a strong correlation between miR-9 expression and miR-9 regulatory activity in NPCs as well as between miR-9 levels/activity, neural migration, and diagnosis. Overexpression of miR-9 was sufficient to ameliorate a previously reported neural migration deficit in SZ NPCs, whereas knockdown partially phenocopied aberrant migration in control NPCs. Unexpectedly, proteomic- and RNA sequencing (RNA-seq)-based analysis revealed that these effects were mediated primarily by small changes in expression of indirect miR-9 targets rather than large changes in direct miR-9 targets; these indirect targets are enriched for migration-associated genes. Together, these data indicate that aberrant levels and activity of miR-9 may be one of the many factors that contribute to SZ risk, at least in a subset of patients.