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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Published in:Molecular neurobiology 2023-06, Vol.60 (6), p.2986-3003
Main Authors: 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
Format: Article
Language:English
Subjects:
Animals
Apoptosis
Apoptosis - genetics
Biomedical and Life Sciences
Biomedicine
Cell Biology
Cell Proliferation - genetics
Cerebellum
Cyclin D2
Cyclin D2 - metabolism
Electron Transport Complex IV - metabolism
Embryogenesis
Exploratory behavior
Homer protein
Homer Scaffolding Proteins - metabolism
Humans
Mice
MicroRNAs - genetics
MicroRNAs - metabolism
miRNA
NADH dehydrogenase
Neurobiology
Neurology
Neurons
Neurons - metabolism
Neurosciences
Spatial discrimination learning
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Summary: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.
ISSN:0893-7648
1559-1182
DOI:10.1007/s12035-023-03239-5