The microRNA-mediated gene regulatory network in the hippocampus and hypothalamus of the aging mouse.

Aging leads to time-dependent functional decline of all major organs. In particular, the aging brain is prone to cognitive decline and several neurodegenerative diseases. Various studies have attempted to understand the aging process and underlying molecular mechanisms by monitoring changes in gene expression in the aging mouse brain using high-throughput sequencing techniques. However, the effect of microRNA (miRNA) on the post-transcriptional regulation of gene expression has not yet been comprehensively investigated. In this study, we performed global analysis of mRNA and miRNA expression simultaneously in the hypothalamus and hippocampus of young and aged mice. We identified aging-dependent differentially expressed genes, most of which were specific either to the hypothalamus or hippocampus. However, genes related to immune response-related pathways were enriched in upregulated differentially expressed genes, whereas genes related to metabolism-related pathways were enriched in downregulated differentially expressed genes in both regions of the aging brain. Furthermore, we identified many differentially expressed miRNAs, including three that were upregulated and three that were downregulated in both the hypothalamus and hippocampus. The two downregulated miRNAs, miR-322-3p, miR-542-3p, and the upregulated protein-encoding coding gene C4b form a regulatory network involved in complement and coagulation cascade pathways in the hypothalamus and hippocampus of the aging brain. These results advance our understanding of the miRNA-mediated gene regulatory network and its influence on signaling pathways in the hypothalamus and hippocampus of the aging mouse brain.

Inhibitory Effects of Acetyloctadecadienediynoic Acid Isolated from Leaves of Dendropanax morbiferus on Viability and Self-Renewal Activity of Glioma Stem-Like Cells.

Glioblastoma (GBM) is one of the most dangerous brain tumors in humans. The median survival of patients with GBM is <18 months. Glioma stem-like cells (GSCs), a small subpopulation of cells with stem cell-like characteristics found within GBM, are regarded as the main cause of GBM malignancy. Therefore, targeting GSCs presents an important therapeutic strategy for reducing the aggressiveness of tumors. In this study, we examined effects of (9Z,16S)-16-O-acetyl-9,17-octadecadiene-12,14-diynoic acid (AODA), a diacetylenic carboxylic acid isolated from leaves of Dendropanax morbiferus, on viability and self-renewal activity of GSCs. AODA substantially decreased GSC growth, causing apoptotic cell death as assessed by Annexin V/PI staining and morphological alterations by optical diffraction tomography. Interestingly, treatment with AODA suppressed ''stem-like features'' in vitro by limiting dilution assays and real-time polymerase chain reaction analysis. In addition, Western blotting revealed that AODA treatment decreased expression levels of phosphorylated AKT and phosphorylated ERK in GSC11 cells. Taken together, our results indicate that AODA could be considered a new therapeutic candidate to target GSCs.