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

© 2023. The Author(s)..

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.

Medienart:

E-Artikel

Erscheinungsjahr:

2023

Erschienen:

2023

Enthalten in:

Zur Gesamtaufnahme - volume:60

Enthalten in:

Molecular neurobiology - 60(2023), 6 vom: 10. Juni, Seite 2986-3003

Sprache:

Englisch

Beteiligte Personen:

Fu, Fang [VerfasserIn]
Chen, Chen [VerfasserIn]
Du, Kun [VerfasserIn]
Li, Lu-Shan [VerfasserIn]
Li, Ru [VerfasserIn]
Lei, Ting-Ying [VerfasserIn]
Deng, Qiong [VerfasserIn]
Wang, Dan [VerfasserIn]
Yu, Qiu-Xia [VerfasserIn]
Yang, Xin [VerfasserIn]
Han, Jin [VerfasserIn]
Pan, Min [VerfasserIn]
Zhen, Li [VerfasserIn]
Zhang, Li-Na [VerfasserIn]
Li, Jian [VerfasserIn]
Li, Fa-Tao [VerfasserIn]
Zhang, Yong-Ling [VerfasserIn]
Jing, Xiang-Yi [VerfasserIn]
Li, Fu-Cheng [VerfasserIn]
Li, Dong-Zhi [VerfasserIn]
Liao, Can [VerfasserIn]

Links:

Volltext

Themen:

Apoptosis
CCND2 protein, human
Cyclin D2
EC 1.9.3.1
Electron Transport Complex IV
HOMER1 protein, human
Homer Scaffolding Proteins
Homer1
Homer1 protein, mouse
Journal Article
MiR-145a-5p
MicroRNAs
NDUFA4 protein, human
Ndufa4
Neuron
Proliferation

Anmerkungen:

Date Completed 25.04.2023

Date Revised 25.04.2023

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1007/s12035-023-03239-5

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM352730498