The miR-17/92 have a general role in cell proliferation and survival during normal development and also during tumorigenesis.34, 45 A recent study of the miR-17/92 cluster and miR-106a/b has shown that miR-19 and miR-92a repress PTEN and TBR2, and suppress the transition from radial glial cells to intermediate progenitors,46 and that miR-17 and 106a/b repress p38α (MAPK14), leading to increased neurogenic and suppressed gliogenic competences in mice.37 The upregulation of p38α (MAPK14) protein seen in the current human study may be owing to the decreased expression of miR-19a/b, members of the miR-17/92 cluster, or miR-185-5p, as they are predicted to target human MAPK14 (TargetScan release 7.0: http://www/targetscan.org/, Supplementary Table 7; Supplementary Figure 6). These miRNAs are reported to show abnormal expression levels in schizophrenic brains.33 Therefore, the underexpression of miR-17/92 cluster members, miR-185-5p and miR-106a/b, and subsequent upregulation of p38α may underlie the observed size reduction of patient-derived neurospheres and the decreased neural differentiation efficiency in patient-derived neurospheres. In support of this theory, abnormal neurogenic-to-gliogenic transition competence balance in patient-derived differentiated cells could be partially recovered by the addition of
