The influence and underlying mechanisms of human adipose-derived stem cells (Hu-ADSCs) on breast cancer cells in the tumor microenvironment remain unclear. Understanding the association between Hu-ADSCs and cancer cells may provide targets for breast cancer treatment and reference for the clinical application of stem cells. Therefore, a Hu-ADSC and breast cancer MCF7 cell coculture system was established to investigate the paracrine effects of Hu-ADSCs on MCF7 cell migration and invasion, in addition to the potential mechanism of action by reverse transcription-quantitative polymerase chain reaction and western blotting. Hu-ADSCs enhanced MCF7 cell migration and invasion by decreasing the expression of epithelial marker E-cadherin, and increasing the expression of interstitial marker N-cadherin and epithelial-mesenchymal transition (EMT) transcription factors in vitro. The EMT effect of cocultured MCF7 cells was inhibited with the addition of anti-transforming growth factor (TGF)-β1 or phosphoinositide 3-kinase (PI3K) inhibitor LY294002, accompanied by a significant decrease in phosphorylated (p)-mothers against decapentaplegic homolog (Smad) and p-protein kinase B (AKT) expression. The data suggested that the paracrine effect of Hu-ADSCs in the tumor microenvironment promoted the EMT of MCF7 cells by cross interacting with the TGF-β/Smad and PI3K/AKT pathways.
Adipocyte deposition is a key feature of age-related thymic involution, but the underlying mechanisms responsible for thymic adiposity remain to be elucidated. In the present study, we utilized rosiglitazone, a potent peroxisome proliferator-activated receptor γ agonist, to induce adipogenic differentiation of OP9-DL1 cells, and detected the metabolomics alterations during adipogenic differentiation by using liquid chromatography-mass spectrometry. The obtained metabolites were further processed by multivariate statistical analysis, including principal component analysis, partial least squares discriminant analysis, and orthogonal projection on latent-structures discriminant analysis. As a result, we identified a total of 33 significantly differential metabolites between dimethyl sulphoxide- and rosiglitazone-treated OP9-DL1 cells, which were closely related to the dysregulation of phospholipid metabolism pathway, oxidative stress, and associated amino acid metabolism. Meanwhile, two pathways including glycerophospholipid metabolism and nitrogen metabolism were significantly perturbed (P < 0.05). Collectively, our results may provide some heuristic guidance for addressing the underlying mechanism of thymic adipogenesis, and future studies are warranted to unravel the functions of these altered metabolites in thymic adipogenesis.
Enantioselective cyclopropanation and C-H insertion reactions of α-substituted vinyl ketones with α-diazoesters have been accomplished using a N,N'-dioxide-scandium(iii) complex catalyst. Various tetrasubstituted cyclopropanes and E-enone derivatives bearing a chiral ester substituent were obtained simultaneously with good yields and excellent enantioselectivities.
Background: Pancreatic cancer is the most aggressive tumor type and is characterized by a poor prognosis.The main cause of treatment failure is the presence of tumor cells resistant to conventional therapies.MicroRNAs (miRNAs) play important roles in modulating the development of pancreatic carcinoma (PC).Methods: In this study, we established radioresistant cell lines from the commonly used human PC parental cell lines. We used high throughput sequencing to screen miRNA expression in both radioresistant and parental cell lines. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to confirm the results. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) biological processes (BPs) were performed to analyze gene set enrichment.Results: In total, 242 differentially expressed miRNAs were identified between these two groups.Compared with the parental line, SW1990-R exhibited with 97 upregulated and 145 downregulated miRNAs. qRT-PCR confirmed five upregulated (miR-497-5p, miR-146b-3p, miR-181a-3p, miR-33a-3p, and miR-32-5p) and five downregulated (miR-7-5p, miR-30b-5p, miR-181a-5p, miR-296-5p, and miR-216a-5p) miRNAs. GO and KEGG enrichment analyses revealed that some of the differentially expressed miRNAs regulated classical functions and pathways, including signal transduction, global and overview map, and immune system.Conclusions: Differential expression of miRNAs in relation to radioresistance suggests that various miRNAs may be predictive biomarkers or therapeutic targets in PC.
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