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Ndufa4 Regulates the Proliferation and Apoptosis of Neurons via miR-145a-5p/Homer1/Ccnd2

The Dandy–Walker malformation (DWM) is characterized by neuron dysregulation in embryonic development; however, the regulatory mechanisms associated with it are unclear. This study aimed to investigate the role of NADH dehydrogenase 1 alpha subcomplex 4 (NDUFA4) in regulating downstream signaling ca...

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Autores principales: Fu, Fang, Chen, Chen, Du, Kun, Li, Lu-shan, Li, Ru, Lei, Ting-ying, Deng, Qiong, Wang, Dan, Yu, Qiu-xia, Yang, Xin, Han, Jin, Pan, Min, Zhen, Li, Zhang, Li-na, Li, Jian, Li, Fa-tao, Zhang, Yong-ling, Jing, Xiang-yi, Li, Fu-cheng, Li, Dong-zhi, Liao, Can
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10122635/
https://www.ncbi.nlm.nih.gov/pubmed/36763283
http://dx.doi.org/10.1007/s12035-023-03239-5
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author Fu, Fang
Chen, Chen
Du, Kun
Li, Lu-shan
Li, Ru
Lei, Ting-ying
Deng, Qiong
Wang, Dan
Yu, Qiu-xia
Yang, Xin
Han, Jin
Pan, Min
Zhen, Li
Zhang, Li-na
Li, Jian
Li, Fa-tao
Zhang, Yong-ling
Jing, Xiang-yi
Li, Fu-cheng
Li, Dong-zhi
Liao, Can
author_facet Fu, Fang
Chen, Chen
Du, Kun
Li, Lu-shan
Li, Ru
Lei, Ting-ying
Deng, Qiong
Wang, Dan
Yu, Qiu-xia
Yang, Xin
Han, Jin
Pan, Min
Zhen, Li
Zhang, Li-na
Li, Jian
Li, Fa-tao
Zhang, Yong-ling
Jing, Xiang-yi
Li, Fu-cheng
Li, Dong-zhi
Liao, Can
author_sort Fu, Fang
collection PubMed
description The Dandy–Walker malformation (DWM) is characterized by neuron dysregulation in embryonic development; however, the regulatory mechanisms associated with it are unclear. This study aimed to investigate the role of NADH dehydrogenase 1 alpha subcomplex 4 (NDUFA4) in regulating downstream signaling cascades and neuronal proliferation and apoptosis. Ndufa4 overexpression promoted the proliferation of neurons and inhibited their apoptosis in vitro, which underwent reverse regulation by the Ndufa4 short hairpin RNAs. Ndufa4-knockout (KO) mice showed abnormal histological alterations in the brain tissue, in addition to impaired spatial learning capacity and exploratory activity. Ndufa4 depletion altered the microRNA expressional profiles of the cerebellum: Ndufa4 inhibited miR-145a-5p expression both in the cerebellum and neurons. miR-145a-5p inhibited the proliferation of neurons and promoted their apoptosis. Ndufa4 promoted and miR-145a-5p inhibited the expression of human homer protein homolog 1 and cyclin D2 in neurons. Thus, Ndufa4 promotes the proliferation of neurons and inhibits their apoptosis by inhibiting miR-145a-5p, which directly targets and inhibits the untranslated regions of Homer1 and Ccnd2 expression. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12035-023-03239-5.
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spelling pubmed-101226352023-04-24 Ndufa4 Regulates the Proliferation and Apoptosis of Neurons via miR-145a-5p/Homer1/Ccnd2 Fu, Fang Chen, Chen Du, Kun Li, Lu-shan Li, Ru Lei, Ting-ying Deng, Qiong Wang, Dan Yu, Qiu-xia Yang, Xin Han, Jin Pan, Min Zhen, Li Zhang, Li-na Li, Jian Li, Fa-tao Zhang, Yong-ling Jing, Xiang-yi Li, Fu-cheng Li, Dong-zhi Liao, Can Mol Neurobiol Article The Dandy–Walker malformation (DWM) is characterized by neuron dysregulation in embryonic development; however, the regulatory mechanisms associated with it are unclear. This study aimed to investigate the role of NADH dehydrogenase 1 alpha subcomplex 4 (NDUFA4) in regulating downstream signaling cascades and neuronal proliferation and apoptosis. Ndufa4 overexpression promoted the proliferation of neurons and inhibited their apoptosis in vitro, which underwent reverse regulation by the Ndufa4 short hairpin RNAs. Ndufa4-knockout (KO) mice showed abnormal histological alterations in the brain tissue, in addition to impaired spatial learning capacity and exploratory activity. Ndufa4 depletion altered the microRNA expressional profiles of the cerebellum: Ndufa4 inhibited miR-145a-5p expression both in the cerebellum and neurons. miR-145a-5p inhibited the proliferation of neurons and promoted their apoptosis. Ndufa4 promoted and miR-145a-5p inhibited the expression of human homer protein homolog 1 and cyclin D2 in neurons. Thus, Ndufa4 promotes the proliferation of neurons and inhibits their apoptosis by inhibiting miR-145a-5p, which directly targets and inhibits the untranslated regions of Homer1 and Ccnd2 expression. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12035-023-03239-5. Springer US 2023-02-10 2023 /pmc/articles/PMC10122635/ /pubmed/36763283 http://dx.doi.org/10.1007/s12035-023-03239-5 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/ Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Fu, Fang
Chen, Chen
Du, Kun
Li, Lu-shan
Li, Ru
Lei, Ting-ying
Deng, Qiong
Wang, Dan
Yu, Qiu-xia
Yang, Xin
Han, Jin
Pan, Min
Zhen, Li
Zhang, Li-na
Li, Jian
Li, Fa-tao
Zhang, Yong-ling
Jing, Xiang-yi
Li, Fu-cheng
Li, Dong-zhi
Liao, Can
Ndufa4 Regulates the Proliferation and Apoptosis of Neurons via miR-145a-5p/Homer1/Ccnd2
title Ndufa4 Regulates the Proliferation and Apoptosis of Neurons via miR-145a-5p/Homer1/Ccnd2
title_full Ndufa4 Regulates the Proliferation and Apoptosis of Neurons via miR-145a-5p/Homer1/Ccnd2
title_fullStr Ndufa4 Regulates the Proliferation and Apoptosis of Neurons via miR-145a-5p/Homer1/Ccnd2
title_full_unstemmed Ndufa4 Regulates the Proliferation and Apoptosis of Neurons via miR-145a-5p/Homer1/Ccnd2
title_short Ndufa4 Regulates the Proliferation and Apoptosis of Neurons via miR-145a-5p/Homer1/Ccnd2
title_sort ndufa4 regulates the proliferation and apoptosis of neurons via mir-145a-5p/homer1/ccnd2
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10122635/
https://www.ncbi.nlm.nih.gov/pubmed/36763283
http://dx.doi.org/10.1007/s12035-023-03239-5
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