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Dysregulation of MicroRNAs Derived from Plasma Extracellular Vesicles in Schizoaffective Disorder

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Abstract

The association between peripheral blood extracellular vesicles (EVs)–derived miRNAs (EVs-miRNAs) and neuropsychiatric diseases has been extensively studied. However, it remains largely unclear about the expression profile of EVs-miRNAs in schizoaffective disorder (SAD) patients. In our study, we isolated the EVs from plasma samples of patients and healthy controls, and then analyzed the expression profiles of EVs-miRNAs through small RNA sequencing. Our results identified 32 differentially expressed (DE) miRNAs (25 upregulated and 7 downregulated) in SAD patients. A module containing 42 miRNAs closely related to SAD was identified by weighted gene co-expression network analysis (WGCNA), among which has-miR-15b-5p, has-miR-301a-3p, has-miR-342-3p, has-miR-219b-5p, and has-miR-145-5p were identified as hub miRNAs. The enrichment analysis showed that the target genes of these 42 miRNAs were significantly enriched in multiple pathways related to neuropathology and located at synapses. A total of 6 DE miRNAs (has-miR-7-5p, has-miR-144-3p, has-miR-155-5p, has-miR-342-3p, has-miR-342-5p, and has-miR-487b-3p) associated with SAD were selected for qRT-PCR verification. The level of has-miR-342-3p in SAD patients was downregulated, and hsa-miR-155-5p was upregulated. Our findings support the hypothesis that dysregulation of EVs-miRNAs in plasma might be involved in the underlying neuropathology of SAD through several biological pathways and provide important preliminary evidence supporting the use of EVs-miRNAs as potential novel biomarkers in SAD.

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Data Availability

All data generated during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

We thank the staff of Shenzhen Pingshan District Center for Disease Control and Prevention for their assistance in the collection of blood samples. Thanks to Dr. Miaobing Zheng from Deakin University for linguistic advice.

Funding

This work was supported by the Research Program of Pingshan Health Commission, Shenzhen, China (No.202189, No.202190), Seed funding of Wuhan University-Duke Kunshan University Joint Research Platform (WHUDKUZZJJ202203), China-Australia Research Cooperation and High-level Talents Training Program in Nutrition and Health Research, China Scholarship Council(2022-No.1007), and the Sichuan International Studies University scientific research project (sisu202215).

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Author notes

  1. Rui Chen and Junxia Shi have contributed equally to this work.

Authors and Affiliations

  1. School of Public Health, Wuhan University, Wuhan, People’s Republic of China

    Rui Chen, Hongguang Yang, Minzhe Zhang & Qiqiang He

  2. Pingshan District Center for Disease Control and Prevention, Shenzhen, People’s Republic of China

    Junxia Shi

  3. College of Language Intelligence, Sichuan International Studies University, Chongqing, People’s Republic of China

    Qiutong Chen

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  1. Rui Chen
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Contributions

Rui Chen: conceptualization; data curation; formal analysis; methodology; software; validation; writing—original draft. Junxia Shi: conceptualization; data curation; visualization; methodology; software. Hongguang Yang: data curation; visualization; formal analysis. Minzhe Zhang: methodology; project administration. Qiutong Chen and Qiqiang He: conceptualization; methodology; writing—review and editing; funding acquisition.

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Correspondence to Qiutong Chen or Qiqiang He.

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The study was carried out in accordance with ethical principles for medical research involving humans (WMA, Declaration of Helsinki). The assessment protocol was approved by the Medical Research Ethics Committee of Wuhan University (2021YF0044).

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Supplementary Information

ESM 1

Table S1. Primer sequences used in qRT-PCR

ESM 2

Table S2. 221highly expressed miRNAs

ESM 3

Table S3. KEGG enrichment analysis for the MEyellow module

ESM 4

Figure S1. Gene ontology enrichment analysis for MEyellow module

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Chen, R., Shi, J., Yang, H. et al. Dysregulation of MicroRNAs Derived from Plasma Extracellular Vesicles in Schizoaffective Disorder. Mol Neurobiol 60, 6373–6382 (2023). https://doi.org/10.1007/s12035-023-03482-w

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