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MiR-4763-3p targeting RASD2as a Potential Biomarker and Therapeutic Target for Schizophrenia
Existing diagnostic methods are limited to observing appearance and demeanor, even though genetic factors play important roles in the pathology of schizophrenia. Indeed, no molecular-level test exists to assist diagnosis, which has limited treatment strategies. To address this serious shortcoming, w...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
JKL International LLC
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9286908/ https://www.ncbi.nlm.nih.gov/pubmed/35855328 http://dx.doi.org/10.14336/AD.2022.0103 |
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author | Wang, Jiao Qi, Wenxin Shi, Hongwei Huang, Lin Ning, Fujiang Wang, Fushuai Wang, Kai Bai, Haotian Wu, Hao Zhuang, Junyi Hong, Huanle Zhou, Haicong Feng, Hu Zhou, Yinping Dong, Naijun Liu, Li Kong, Yanyan Xie, Jiang Zhao, Robert Chunhua |
author_facet | Wang, Jiao Qi, Wenxin Shi, Hongwei Huang, Lin Ning, Fujiang Wang, Fushuai Wang, Kai Bai, Haotian Wu, Hao Zhuang, Junyi Hong, Huanle Zhou, Haicong Feng, Hu Zhou, Yinping Dong, Naijun Liu, Li Kong, Yanyan Xie, Jiang Zhao, Robert Chunhua |
author_sort | Wang, Jiao |
collection | PubMed |
description | Existing diagnostic methods are limited to observing appearance and demeanor, even though genetic factors play important roles in the pathology of schizophrenia. Indeed, no molecular-level test exists to assist diagnosis, which has limited treatment strategies. To address this serious shortcoming, we used a bioinformatics approach to identify 61 genes that are differentially expressed in schizophrenia patients compared with healthy controls. In particular, competing endogenous RNA network revealed the important role of the gene RASD2, which is regulated by miR-4763-3p. Indeed, analysis of blood samples confirmed that RASD2 is downregulated in schizophrenia patients. Moreover, positron emission tomography data collected for 44 human samples identified the prefrontal and temporal lobes as potential key brain regions in schizophrenia patients. Mechanistic studies indicated that miR-4763-3p inhibits RASD2 by base-pairing with the 3’ untranslated region of RASD2 mRNA. Importantly, RASD2 has been shown to interact with β-arrestin2, which contributes to the regulation of the DRD2-dependent CREB response element-binding protein pathway in the dopamine system. Finally, results obtained with a mouse model of schizophrenia revealed that inhibition of miR-4763-3p function alleviated anxiety symptoms and improved memory. The dopamine transporters in the striatal regions were significantly reduced in schizophrenia model mice as compared with wild-type mice, suggesting that inhibition of miR-4763-3p can lessen the symptoms of schizophrenia. Our findings demonstrate that miR-4763-3p may target RASD2 mRNA and thus may serve as a potential biomarker and therapeutic target for schizophrenia, providing a theoretical foundation for further studies of the molecular basis of this disease. |
format | Online Article Text |
id | pubmed-9286908 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | JKL International LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-92869082022-07-18 MiR-4763-3p targeting RASD2as a Potential Biomarker and Therapeutic Target for Schizophrenia Wang, Jiao Qi, Wenxin Shi, Hongwei Huang, Lin Ning, Fujiang Wang, Fushuai Wang, Kai Bai, Haotian Wu, Hao Zhuang, Junyi Hong, Huanle Zhou, Haicong Feng, Hu Zhou, Yinping Dong, Naijun Liu, Li Kong, Yanyan Xie, Jiang Zhao, Robert Chunhua Aging Dis Original Article Existing diagnostic methods are limited to observing appearance and demeanor, even though genetic factors play important roles in the pathology of schizophrenia. Indeed, no molecular-level test exists to assist diagnosis, which has limited treatment strategies. To address this serious shortcoming, we used a bioinformatics approach to identify 61 genes that are differentially expressed in schizophrenia patients compared with healthy controls. In particular, competing endogenous RNA network revealed the important role of the gene RASD2, which is regulated by miR-4763-3p. Indeed, analysis of blood samples confirmed that RASD2 is downregulated in schizophrenia patients. Moreover, positron emission tomography data collected for 44 human samples identified the prefrontal and temporal lobes as potential key brain regions in schizophrenia patients. Mechanistic studies indicated that miR-4763-3p inhibits RASD2 by base-pairing with the 3’ untranslated region of RASD2 mRNA. Importantly, RASD2 has been shown to interact with β-arrestin2, which contributes to the regulation of the DRD2-dependent CREB response element-binding protein pathway in the dopamine system. Finally, results obtained with a mouse model of schizophrenia revealed that inhibition of miR-4763-3p function alleviated anxiety symptoms and improved memory. The dopamine transporters in the striatal regions were significantly reduced in schizophrenia model mice as compared with wild-type mice, suggesting that inhibition of miR-4763-3p can lessen the symptoms of schizophrenia. Our findings demonstrate that miR-4763-3p may target RASD2 mRNA and thus may serve as a potential biomarker and therapeutic target for schizophrenia, providing a theoretical foundation for further studies of the molecular basis of this disease. JKL International LLC 2022-07-11 /pmc/articles/PMC9286908/ /pubmed/35855328 http://dx.doi.org/10.14336/AD.2022.0103 Text en copyright: © 2022 Wang et al. https://creativecommons.org/licenses/by/2.0/this is an open access article distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. |
spellingShingle | Original Article Wang, Jiao Qi, Wenxin Shi, Hongwei Huang, Lin Ning, Fujiang Wang, Fushuai Wang, Kai Bai, Haotian Wu, Hao Zhuang, Junyi Hong, Huanle Zhou, Haicong Feng, Hu Zhou, Yinping Dong, Naijun Liu, Li Kong, Yanyan Xie, Jiang Zhao, Robert Chunhua MiR-4763-3p targeting RASD2as a Potential Biomarker and Therapeutic Target for Schizophrenia |
title | MiR-4763-3p targeting RASD2as a Potential Biomarker and Therapeutic Target for Schizophrenia |
title_full | MiR-4763-3p targeting RASD2as a Potential Biomarker and Therapeutic Target for Schizophrenia |
title_fullStr | MiR-4763-3p targeting RASD2as a Potential Biomarker and Therapeutic Target for Schizophrenia |
title_full_unstemmed | MiR-4763-3p targeting RASD2as a Potential Biomarker and Therapeutic Target for Schizophrenia |
title_short | MiR-4763-3p targeting RASD2as a Potential Biomarker and Therapeutic Target for Schizophrenia |
title_sort | mir-4763-3p targeting rasd2as a potential biomarker and therapeutic target for schizophrenia |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9286908/ https://www.ncbi.nlm.nih.gov/pubmed/35855328 http://dx.doi.org/10.14336/AD.2022.0103 |
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