MicroRNA-7/Shank3 axis involved in schizophrenia pathogenesis

Abstract This study aimed to identify the difference of microRNA-7 (miR-7) expression levels between schizophrenia patients and healthy controls and to investigate the regulatory effects of miR-7 on the SHANK3 gene in schizophrenia. miR-7 levels in plasma were detected by quantitative polymerase chain reactions (qPCR) in 50 schizophrenia patients and 50 healthy controls. The hippocampal neuron cell line, HT22 , was transfected with lentiviral vector overexpressing or knocking-down miR-7, and the expression levels of SHANK3 mRNA and Shank3 protein were measured by qPCR and immunofluorescence. A luciferase assay was carried out to analyze the regulatory effects of miR-7 on SHANK3. Circulating miR-7 level was significantly increased in schizophrenia patients ( p = 0.022). Overexpression of miR-7 suppressed the expression of SHANK3 while the levels of SHANK3 mRNA and Shank protein were significantly increased by miR-7 knockdown. We conclude that miR-7 binds to 3-prime untranslated regions of SHANK3 mRNA and causes the alteration of neuronal morphology and function, potentially playing a crucial role in the pathophysiological process of schizophrenia.