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.