Peripheral Blood Exosomal miR-184-3p in Methamphetamine Use Disorder: Biomarker Potential and CRTC1-Mediated Neuroadaptation

The neurobiological mechanisms underlying methamphetamine use disorder (MUD) remain elusive, and specific treatment modalities as well as diagnostic markers are scarce. The emergence of exosomes has opened up possibilities for developing diagnostic and assessment biomarkers for neuropsychiatric diso...

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Main Authors: Yan Zhao, Zhuoming Zhao, Qianqian Sun, Hang Su, Tianzhen Chen, Xiaomin Xu, Xiaotong Li, Sai Shi, Jiang Du, Haifeng Jiang, Min Zhao
Format: Article
Language:English
Published: MDPI AG 2025-06-01
Series:Current Issues in Molecular Biology
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Online Access:https://www.mdpi.com/1467-3045/47/7/479
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author Yan Zhao
Zhuoming Zhao
Qianqian Sun
Hang Su
Tianzhen Chen
Xiaomin Xu
Xiaotong Li
Sai Shi
Jiang Du
Haifeng Jiang
Min Zhao
author_facet Yan Zhao
Zhuoming Zhao
Qianqian Sun
Hang Su
Tianzhen Chen
Xiaomin Xu
Xiaotong Li
Sai Shi
Jiang Du
Haifeng Jiang
Min Zhao
author_sort Yan Zhao
collection DOAJ
description The neurobiological mechanisms underlying methamphetamine use disorder (MUD) remain elusive, and specific treatment modalities as well as diagnostic markers are scarce. The emergence of exosomes has opened up possibilities for developing diagnostic and assessment biomarkers for neuropsychiatric disorders. Hence, the present study aimed to preliminarily explore the alterations in exosomal miRNA expression in MUD patients and the potential mechanisms involved in MUD. First, miRNA sequencing and RT-qPCR were used to verify the differential expression of peripheral blood exosomal miR-184-3p and miR-4433a-5p in MUD patients. Subsequently, the diagnostic ability of these two miRNAs for MUD was evaluated using ROC analysis. Finally, the regulatory relationship between miRNA-184-3p and its downstream target gene CRTC1 was verified by dual luciferase reporter assay. The results demonstrated that exosomal miR-184-3p and miR-4433a-5p were markedly decreased in MUD patients. However, the expression level of miR-4433a-5p was influenced by anxiety-depressive symptoms. The ROC analysis revealed that the AUCs of exosomal miRNA-184-3p in the training and validation sets of MUD patients were 0.902 and 0.823, respectively. In conclusion, exosomal miR-184-3p levels in peripheral blood may be a potential biomarker for the diagnosis and assessment of MUD, and it may be involved in the pathophysiological process of MUD through the targeted regulation of the CRTC1/CREB pathway.
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spelling doaj-art-9fa82672a97a4870897e110de7ea68572025-08-20T03:35:27ZengMDPI AGCurrent Issues in Molecular Biology1467-30371467-30452025-06-0147747910.3390/cimb47070479Peripheral Blood Exosomal miR-184-3p in Methamphetamine Use Disorder: Biomarker Potential and CRTC1-Mediated NeuroadaptationYan Zhao0Zhuoming Zhao1Qianqian Sun2Hang Su3Tianzhen Chen4Xiaomin Xu5Xiaotong Li6Sai Shi7Jiang Du8Haifeng Jiang9Min Zhao10Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, ChinaShanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, ChinaShanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, ChinaShanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, ChinaShanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, ChinaShanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, ChinaShanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, ChinaShanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, ChinaShanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, ChinaShanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, ChinaShanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, ChinaThe neurobiological mechanisms underlying methamphetamine use disorder (MUD) remain elusive, and specific treatment modalities as well as diagnostic markers are scarce. The emergence of exosomes has opened up possibilities for developing diagnostic and assessment biomarkers for neuropsychiatric disorders. Hence, the present study aimed to preliminarily explore the alterations in exosomal miRNA expression in MUD patients and the potential mechanisms involved in MUD. First, miRNA sequencing and RT-qPCR were used to verify the differential expression of peripheral blood exosomal miR-184-3p and miR-4433a-5p in MUD patients. Subsequently, the diagnostic ability of these two miRNAs for MUD was evaluated using ROC analysis. Finally, the regulatory relationship between miRNA-184-3p and its downstream target gene CRTC1 was verified by dual luciferase reporter assay. The results demonstrated that exosomal miR-184-3p and miR-4433a-5p were markedly decreased in MUD patients. However, the expression level of miR-4433a-5p was influenced by anxiety-depressive symptoms. The ROC analysis revealed that the AUCs of exosomal miRNA-184-3p in the training and validation sets of MUD patients were 0.902 and 0.823, respectively. In conclusion, exosomal miR-184-3p levels in peripheral blood may be a potential biomarker for the diagnosis and assessment of MUD, and it may be involved in the pathophysiological process of MUD through the targeted regulation of the CRTC1/CREB pathway.https://www.mdpi.com/1467-3045/47/7/479methamphetamineexosomemicroRNAbiomarkerCRTC1
spellingShingle Yan Zhao
Zhuoming Zhao
Qianqian Sun
Hang Su
Tianzhen Chen
Xiaomin Xu
Xiaotong Li
Sai Shi
Jiang Du
Haifeng Jiang
Min Zhao
Peripheral Blood Exosomal miR-184-3p in Methamphetamine Use Disorder: Biomarker Potential and CRTC1-Mediated Neuroadaptation
Current Issues in Molecular Biology
methamphetamine
exosome
microRNA
biomarker
CRTC1
title Peripheral Blood Exosomal miR-184-3p in Methamphetamine Use Disorder: Biomarker Potential and CRTC1-Mediated Neuroadaptation
title_full Peripheral Blood Exosomal miR-184-3p in Methamphetamine Use Disorder: Biomarker Potential and CRTC1-Mediated Neuroadaptation
title_fullStr Peripheral Blood Exosomal miR-184-3p in Methamphetamine Use Disorder: Biomarker Potential and CRTC1-Mediated Neuroadaptation
title_full_unstemmed Peripheral Blood Exosomal miR-184-3p in Methamphetamine Use Disorder: Biomarker Potential and CRTC1-Mediated Neuroadaptation
title_short Peripheral Blood Exosomal miR-184-3p in Methamphetamine Use Disorder: Biomarker Potential and CRTC1-Mediated Neuroadaptation
title_sort peripheral blood exosomal mir 184 3p in methamphetamine use disorder biomarker potential and crtc1 mediated neuroadaptation
topic methamphetamine
exosome
microRNA
biomarker
CRTC1
url https://www.mdpi.com/1467-3045/47/7/479
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