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

Abstract

Our previous study demonstrated that the expression of sodium channel voltage-gated beta 2 (ScN2B) increased with aging in senescence-accelerated 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 miR-449a, which was downregulated in the hippocampus. Previous studies demonstrated that miR-449a is involved in the occurrence and progression of aging by regulating a variety of target genes. Therefore, it was hypothesized that miR-449a may be involved in the process of brain aging by targeting ScN2B. To verify this hypothesis, the following experiments were conducted: A reverse transcription-quantitative polymerase chain reaction assay revealed that the expression level of miR-449a was significantly decreased in the prefrontal cortex and hippocampus of 12-month old SAMP8 mice; a dual-luciferase reporter assay verified that miR-449a regulated ScN2B expression by binding to the 3'-UTR 'seed region'; an anti-Ago co-immunoprecipitation combined with Affymetrix microarray analyses demonstrated that the target mRNA highly enriched with Ago-miRNPs was confirmed to be ScN2B. Finally, overexpression of miR-449a or inhibition of ScN2B promoted the extension of hippocampal neurons in vitro. The results of the present study suggested that miR-449a was downregulated in the prefrontal cortex and hippocampus of SAMP8 mice and may regulate the process of brain aging by targeting ScN2B.

Long non‑coding RNA NR2F1‑AS1 facilitates the osteosarcoma cell malignant phenotype via the miR‑485‑5p/miR‑218‑5p/BIRC5 axis

“…Human OS cell lines (HOS, MG63 and U2OS) and a normal osteoblast cell line (hFOB1. 19) were obtained from the Chinese Academy of Sciences Cell Bank. The OS cells (HOS, MG63 and U2OS) were cultured in RPMI-1640 medium (Sangon Biotech Co., Ltd.) with 10% fetal bovine serum (FBS; Hyclone; Thermo Fisher Scientific, Inc.) in a 5% CO 2 atmosphere at 37˚C.…”

“…A number of studies have demonstrated that miRNAs exhibit roles in numerous biological processes by regulating their mRNA targets, including in cell development, tumorigenesis, cell differentiation and aging ( 17 – 19 ). In OS, the miRNA expression profile has been extensively studied, and a variety of miRNAs has been identified to play a role in OS, such as miR-422a, miR-145 and miR-194 ( 20 ).…”

High-Throughput Sequencing of BACHD Mice Reveals Upregulation of Neuroprotective miRNAs at the Pre-Symptomatic Stage of Huntington’s Disease

“…Microarray analysis identified a down-regulation of miR-449a-5p and miR-34a-5p in prefrontal cortex samples of a senescence-accelerated mouse model (SAMP8) and further analysis correlated this down-regulation with an increase of sodium channel subunit beta-2 (SCN2B) expression levels. In addition, miR-449a-5p upregulation or SCN2B downregulation increased neurite extension of cultured neurons, suggesting that miR-449a might play an important role in neuronal growth and associated progression of aging by targeting SCN2B ( Tan et al., 2020 ). Other studies revealed that miR-34/449 are involved in specific developmental alteration on brain substrates.…”

Lamivudine improves cognitive decline in SAMP8 mice: Integrating in vivo pharmacological evaluation and network pharmacology

“…The SAMP8 mice were derived from the SAM‐P/2 line as a rapidly ageing mouse model of dementia. A previous study showed that the SAMP8 mice exhibited age‐related cognitive decline with a short lifespan, showing progressive learning and memory deficits as well as neuropathological hallmarks of dementia in the prefrontal cortex and hippocampus 31 . The lifespan of SAMP8 mice is almost half of that of SAMR1, which were used as the controls for the SAMP8 32 .…”