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MicroRNA Profiles and Differential Expression in Normal Skin Samples from the Uyghur and Han Populations in Xinjiang

ABSTRACT: This study investigated the microRNA (miRNA) expression profiles in normal skin samples from the Uyghur and Han populations in Xinjiang and analyzed the miRNA expression differences between the two populations. The 7th generation miRCURYTM LNA Array kit (containing 3100 probes) was used to detect the miRNA expression in 10 Uyghur and 10 Han normal skin samples and to compare the miRNA expression differences between the two populations. A total of 2041 miRNAs were present in normal Uyghur and Han skin samples. In particular, 2039 miRNAs were present in normal Uyghur skin, of which 295 miRNAs were expressed more than 2.0-fold and 1461 miRNAs were expressed less than 0.5-fold of the average value. Moreover, 2041 miRNAs were expressed in normal Han skin, of which 279 miRNAs were expressed more than 2.0-fold and 1414 miRNAs were expressed less than 0.5-fold of the average value. Considering both populations together, 228 miRNAs were expressed more than 2.0-fold and 1353 miRNAs were expressed less than 0.5-fold of the average value. In the Han population, 76 miRNAs were upregulated and 171 miRNAs were downregulated compared with the Uyghur population (p < 0.05). A total of 13 miRNAs had fold changes that were greater than 10, and 9 miRNAs had fold changes that were between 3 and 10. The upregulated miRNAs were miR-1, miR-106b-5p, miR-1915-5p, miR-200c-3p, miR-221-3p, miR-222-3p, miR-3139, miR-4802-3p, miR-507, miR-541-3p, miR-876-3p, and kshv-miR-K12-2-5p. The downregulated miRNAs were miR-1207-3p, miR-206, miR-2116-5p, miR-3667-5p, miR-374b-3p, miR-4423-5p, miR-4450, miR-4468, miR-542-3p, miR-548ao-3p, and miR-553. Specific miRNA expression patterns were observed in normal Uyghur and Han skin samples, and the miRNA expression patterns differed significantly between the two populations.

ORGANISM(S): Merkel cell polyomavirus Human alphaherpesvirus 2 Betapolyomavirus hominis Human alphaherpesvirus 1 Cytomegalovirus Lymphocryptovirus JC polyomavirus Betapolyomavirus macacae Human immunodeficiency virus 1 Homo sapiens Rhadinovirus

PROVIDER: GSE62354 | GEO | 2014/10/16

SECONDARY ACCESSION(S): PRJNA263896

REPOSITORIES: GEO

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Project description:Background: Newer 3D culturing approaches are a promising way to better mimic the in vivo tumor microenvironment and to study the interactions between the heterogeneous cell populations of glioblastoma multiforme. Like many other tumors, glioblastoma uses extracellular vesicles as an intercellular communication system to prepare surrounding tissue for invasive tumor growth. However, little is known about the effects of 3D culture on extracellular vesicles. The aim of this study was to comprehensively characterise extracellular vesicles in 3D organoid models and compare them to conventional 2D cell culture systems.Methods: Primary glioblastoma cells were cultured as 2D and 3D organoid models. Extracellular vesicles were obtained by precipitation and immunoaffinity, with the latter allowing targeted isolation of the CD9/CD63/CD81 vesicle subpopulation. Comprehensive vesicle characterisation was performed and miRNA expression profiles were generated by smallRNA-sequencing. In silico analysis of differentially regulated miRNAs was performed to identify mRNA targets and corresponding signaling pathways. The tumor cell media and extracellular vesicle proteome were analysed by high-resolution mass spectrometry.Results: We observed an increased concentration of extracellular vesicles in 3D organoid cultures. Differential gene expression analysis further revealed the regulation of twelve miRNAs in 3D tumor organoid cultures (with nine miRNAs down and three miRNAs upregulated). MiR-23a-3p, known to be involved in glioblastoma invasion, was significantly increased in 3D. MiR-7-5p, which counteracts glioblastoma malignancy, was significantly decreased. Moreover, we identified four miRNAs (miR- 323a-3p, miR-382-5p, miR-370-3p, miR-134-5p) located within the DLK1-DIO3 domain, a cancer associated genomic region, suggesting a possible importance of this region in glioblastoma progression. Overrepresentation analysis identified alterations of extracellular vesicle cargo in 3D organoids, including representation of several miRNA targets and proteins primarily implicated in the immune response.Conclusion: Our results show that 3D glioblastoma organoid models secrete extracellular vesicles with an altered cargo compared to corresponding conventional 2D cultures. Extracellular vesicles from 3D cultures were found to contain signaling molecules associated with the immune regulatory signaling pathways and as such could potentially change the surrounding microenvironment towards tumor progression and immunosuppressive conditions. These findings suggest the use of 3D glioblastoma models for further clinical biomarker studies as well as investigation of new therapeutic options.

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MicroRNA Profiles and Differential Expression in Normal Skin Samples from the Uyghur and Han Populations in Xinjiang

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