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. 2019 Feb;98(8):e14332.
doi: 10.1097/MD.0000000000014332.

Screening of schizophrenia associated miRNAs and the regulation of miR-320a-3p on integrin β1

Yuhan Wang  1 , Jie Wang, Tianhong Guo, Ying Peng, Kaizheng Wang, Kezhen Bai, Yuanshuai Huang
Affiliations

Screening of schizophrenia associated miRNAs and the regulation of miR-320a-3p on integrin β1

Yuhan Wang et al. Medicine (Baltimore). 2019 Feb.

Abstract

Schizophrenia is one of the most severe chronic psychiatric disorders, which lacks of objective and effective diagnosis and observation indicators.In this work, the serum miRNA profiles of schizophrenic patients were analyzed. Targets of abnormal miRNAs, and their regulatory mechanisms were studied. A miRNA array was used to analyze the serum from 3 schizophrenic patients without treatment, 3 clinically cured patients and 3 healthy controls. The findings from the array were confirmed by real-time PCR in a larger cohort, including 59 patients and 60 healthy controls. The candidate miRNAs were analyzed using bioinformatics tools. Their potential targets were studied through in vitro cellular experiments.MiR-320a-3p and miR-320b were found to be down-regulated in patients compared with cured patients and controls in the miRNA array, which was also confirmed by real-time PCR in the larger cohort. Integrin β1 (ITG β1) was found to be one of the targets of miR-320a-3p. An enzyme-linked immune sorbent assay demonstrated that the ITG β1 concentration increased significantly in the patients' serum, and the in vitro study confirmed that miR-320a-3p targeted the 3' UTR of ITG β1 mRNA and reduced its expression.Our results demonstrated that the regulatory effect of miR-320a-3p on its target ITG β1 might play an important role in schizophrenia pathogenesis, which could be a potential pathway for schizophrenia diagnosis and therapy.

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Conflict of interest statement

The authors have no conflicts of interest to disclose.

Figures

Figure 1
Figure 1
ChIP results and quantitative PCR validation. Notes: A: heatmap of ChIP result; B: part of the ChIP results shown via a bar chart; C: quantitative analysis of miR-320a-3p in Sz and H serum specimens; D: quantitative analysis of miR-320b in Sz and H serum specimens. Sz: schizophrenic patients without treatment; Sz-H: cured schizophrenic patients; H: healthy adults.∗P < .05.
Figure 2
Figure 2
miR-320a-3p binding sites and ITG β1 concentrations in the different groups. Notes: A: diagram of miR-320a-3p binding sites in the ITG β1 3′ UTR; B: ITG β1 concentrations in Sz and H serum specimens.
Figure 3
Figure 3
Functional study of the miRNAs of interest. Notes: A: ITG β1 mRNA levels in cells after treatment; B: western blot results of cells after treatment. ∗P < .05.
Figure 4
Figure 4
Luciferase activity assay.
See this image and copyright information in PMC

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