Abstract |
Dysfunctions of neural stem cells (NSCs) often lead to a variety of neurological diseases. Thus, therapies based on NSCs have gained increasing attention recently. It has been documented that microRNA (miR)-421 represses the autophagy and apoptosis of mouse hippocampal neurons and confers a role in the repair of ischemic brain injury (IBI). Herein, we aimed to illustrate the effects of miR-421 on NSC self-renewal. The downstream factors of miR-421 were predicted initially, followed by gain- and loss-of-function assays to examine their effects on NSC self-renewal. Immunoprecipitation and dual luciferase assays were conducted to validate the interaction among miR-421, PTEN-induced putative kinase 1 (PINK1), HDAC3, and forkhead box O3 (FOXO3). A mouse model with IBI was developed to substantiate the impact of the miR-421/PINK1/HDAC3/FOXO3 axis on NSC self-renewal. The expression of miR-421 was downregulated during differentiation of human embryonic NSCs, and miR-421 overexpression accelerated NSC self-renewal. Besides, miR-421 targeted PINK1 and restricted its expression in NSCs and further suppressed HDAC3 phosphorylation and enhanced FOXO3 acetylation. In conclusion, our data elucidated that miR-421 overexpression may facilitate NSC self-renewal through the PINK1/HDAC3/FOXO3 axis, which may provide potential therapeutic targets for the development of novel therapies for IBI.
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Authors | Jiaoying Jia, Ming Wang, Min Liu, Zhigang Tan, Yan Cui, Mengqiang Yu |
Journal | Frontiers in cell and developmental biology
(Front Cell Dev Biol)
Vol. 9
Pg. 621187
( 2021)
ISSN: 2296-634X [Print] Switzerland |
PMID | 34354990
(Publication Type: Journal Article)
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Copyright | Copyright © 2021 Jia, Wang, Liu, Tan, Cui and Yu. |