Altered expression of microRNA-223 in the plasma of patients with first-episode schizophrenia and its possible relation to neuronal migration-related genes
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Published:2019-11-11
Issue:1
Volume:9
Page:
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ISSN:2158-3188
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Container-title:Translational Psychiatry
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language:en
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Short-container-title:Transl Psychiatry
Author:
Zhao Zhilei, Jinde Seiichiro, Koike ShinsukeORCID, Tada Mariko, Satomura Yoshihiro, Yoshikawa Akane, Nishimura Yukika, Takizawa Ryu, Kinoshita Akihide, Sakakibara Eisuke, Sakurada Hanako, Yamagishi Mika, Nishimura Fumichika, Inai Aya, Nishioka Masaki, Eriguchi Yosuke, Araki Tsuyoshi, Takaya Atsuhiko, Kan Chiemi, Umeda Maki, Shimazu Akihito, Hashimoto Hideki, Bundo Miki, Iwamoto KazuyaORCID, Kakiuchi Chihiro, Kasai Kiyoto
Abstract
Abstract
Recent studies have shown that microRNAs (miRNAs) play a role as regulators of neurodevelopment by modulating gene expression. Altered miRNA expression has been reported in various psychiatric disorders, including schizophrenia. However, the changes in the miRNA expression profile that occur during the initial stage of schizophrenia have not been fully investigated. To explore the global alterations in miRNA expression profiles that may be associated with the onset of schizophrenia, we first profiled miRNA expression in plasma from 17 patients with first-episode schizophrenia and 17 healthy controls using microarray analysis. Among the miRNAs that showed robust changes, the elevated expression of has-miR-223-3p (miR-223) was validated via quantitative reverse transcription-polymerase chain reaction (qRT-PCR) using another independent sample set of 21 schizophrenia patients and 21 controls. To identify the putative targets of miR-223, we conducted a genome-wide gene expression analysis in neuronally differentiated SK-N-SH cells with stable miR-223 overexpression and an in silico analysis. We found that the mRNA expression levels of four genes related to the cytoskeleton or cell migration were significantly downregulated in miR-223-overexpressing cells, possibly due to interactions with miR-223. The in silico analysis suggested the presence of miR-223 target sites in these four genes. Lastly, a luciferase assay confirmed that miR-223 directly interacted with the 3′ untranslated regions (UTRs) of all four genes. Our results reveal an increase in miR-223 in plasma during both the first episode and the later stage of schizophrenia, which may affect the expression of cell migration-related genes targeted by miR-223.
Funder
a research grant from Research Group for Schizophrenia MEXT | Japan Society for the Promotion of Science Japan Agency for Medical Research and Development the UTokyo Center for Integrative Science of Human Behavior
Publisher
Springer Science and Business Media LLC
Subject
Biological Psychiatry,Cellular and Molecular Neuroscience,Psychiatry and Mental health
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