MicroRNAs (miRNA) are small noncoding RNAs that regulate gene expression in human diseases, including lung cancer. miRNAs have oncogenic and nononcogenic functions in lung cancer. In this study, we report the identification of a novel miRNA, miR-7515, from lung cancer cells. The novel miR-7515 was characterized using various predictive programs and experimental methods. miR-7515 was able to forming a stem-loop structure and its sequence was conserved in mammals. The expression level of miR-7515 in lung cancer cells and tissues was profiled using TaqMan miRNA assays. miR-7515 was downregulated in lung cancer compared with normal human lung cells and tissues. The target of miR-7515 was determined using a dual luciferase reporter assay.
IntroductionThe first microRNA (miRNA) was discovered in Caenorhabditis elegans, (1, 2) and there are currently more than 1,500 human miRNAs listed in miRBase (http://microrna.sanger.ac.uk/index.shtml; ref. 3). miRNAs are endogenous noncoding RNAs that are 18 to 25 nucleotides (nt) in length and are derived from 60 to 80 nt precursor miRNAs refs. 4,5). The stepwise processing of miRNAs requires the double strand-specific ribonuclease (Drosha), the RNase III enzyme Dicer, and the
MicroRNAs (miRNAs) are a class of small noncoding RNAs that negatively regulate gene expression through binding to 3' untranslated region. We identified and characterized the novel miRNA, miR-7641, in human mesenchymal stem cells. The expression of miR-7641 was downregulated during differentiation from human embryonic stem cells to endothelial cells. The CXCL1, a member of the CXC chemokine family, is known as promoting neovascularization by binding G-protein coupled receptors and is related to endothelial cells biogenesis such as angiogenesis, and it was predicted as target gene of miR-7641 by computerized analysis and the luciferase reporter assay. The miR-7641 significantly suppressed CXCL1 of transcriptional and post-translational levels. These data suggest that miR-7641 might be related with differentiation of human endothelial cells.
Background
Stem cell transplantation is a fascinating therapeutic approach for the treatment of many neurodegenerative disorders; however, clinical trials using stem cells have not been as effective as expected based on preclinical studies. The aim of this study is to validate the hypothesis that human neural crest-derived nasal turbinate stem cells (hNTSCs) are a clinically promising therapeutic source of adult stem cells for the treatment of Alzheimer’s disease (AD).
Methods
hNTSCs were evaluated in comparison with human bone marrow-derived mesenchymal stem cells (hBM-MSCs) according to the effect of transplantation on AD pathology, including PET/CT neuroimaging, immune status indicated by microglial numbers and autophagic capacity, neuronal survival, and cognition, in a 5 × FAD transgenic mouse model of AD.
Results
We demonstrated that hNTSCs showed a high proliferative capacity and great neurogenic properties in vitro. Compared with hBM-MSC transplantation, hNTSC transplantation markedly reduced Aβ42 levels and plaque formation in the brains of the 5 × FAD transgenic AD mice on neuroimaging, concomitant with increased survival of hippocampal and cortex neurons. Moreover, hNTSCs strongly modulated immune status by reducing the number of microglia and the expression of the inflammatory cytokine IL-6 and upregulating autophagic capacity at 7 weeks after transplantation in AD models. Notably, compared with transplantation of hBM-MSCs, transplantation of hNTSCs significantly enhanced performance on the Morris water maze, with an increased level of TIMP2, which is necessary for spatial memory in young mice and neurons; this difference could be explained by the high engraftment of hNTSCs after transplantation.
Conclusion
The reliable evidence provided by these findings reveals a promising therapeutic effect of hNTSCs and indicates a step forward the clinical application of hNTSCs in patients with AD.
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