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Publication : MicroRNA‑449a regulates the progression of brain aging by targeting SCN2B in SAMP8 mice.

First Author  Tan YX Year  2020
Journal  Int J Mol Med Volume  45
Issue  4 Pages  1091-1102
PubMed ID  32124967 Mgi Jnum  J:298554
Mgi Id  MGI:6480247 Doi  10.3892/ijmm.2020.4502
Citation  Tan YX, et al. (2020) MicroRNA449a regulates the progression of brain aging by targeting SCN2B in SAMP8 mice. Int J Mol Med 45(4):1091-1102
abstractText  Our previous study demonstrated that the expression of sodium channel voltagegated beta 2 (SCN2B) increased with aging in senescenceaccelerated mouse prone 8 (SAMP8) mice, and was identified to be associated with a decline in learning and memory, while the underlying mechanism is unclear. In the present study, multiple differentially expressed miRNAs, which may be involved in the process of aging by regulating target genes, were identified in the prefrontal cortex and hippocampus of SAMP8 mice though miRNA microarray analysis. Using bioinformatics prediction, SCN2B was identified to be one of the potential target genes of miR449a, which was downregulated in the hippocampus. Previous studies demonstrated that miR449a is involved in the occurrence and progression of aging by regulating a variety of target genes. Therefore, it was hypothesized that miR449a may be involved in the process of brain aging by targeting SCN2B. To verify this hypothesis, the following experiments were conducted: A reverse transcriptionquantitative polymerase chain reaction assay revealed that the expression level of miR449a was significantly decreased in the prefrontal cortex and hippocampus of 12month old SAMP8 mice; a dualluciferase reporter assay verified that miR449a regulated SCN2B expression by binding to the 3'UTR 'seed region'; an antiAgo coimmunoprecipitation combined with Affymetrix microarray analyses demonstrated that the target mRNA highly enriched with AgomiRNPs was confirmed to be SCN2B. Finally, overexpression of miR449a or inhibition of SCN2B promoted the extension of hippocampal neurons in vitro. The results of the present study suggested that miR449a was downregulated in the prefrontal cortex and hippocampus of SAMP8 mice and may regulate the process of brain aging by targeting SCN2B.
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