Dataset Information

Identification and differential expression of microRNAs in 1, 25-dihydroxyvitamin D3-induced osteogenic differentiation of human adipose-derived mesenchymal stem cells.

ABSTRACT: The aim of this study was to identify specific microRNAs (miRNAs) and their regulatory roles in the process of 1, 25-dihydroxyvitamin D3-induced (VD3-induced) osteogenic differentiation of human adipose-derived Mesenchymal stem cells (hAMSCs). The differentially expressed miRNAs in VD3-induced hAMSCs was examined. The putative target genes of these miRNAs were predicted. A total of 76 conserved miRNAs, including 18 miRNAs were significantly up-regulated and 58 miRNAs were significantly downregulated, and significantly differentially expressed between the two samples. The expression of 4 upregulated miRNAs (miR-1-3p, miR-1247-5p, miR-217, and miRNA-483) and 5 downregulated miRNAs (miR-1284, miR-218, miR-582-3p, miR-187-3p, and miRNA-122-5p) were verified. The highly enriched GOs and KEGG pathway showed target genes of these miRNAs were significantly involved in multiple biological processes (signal transduction, cell differentiation, cell adhesion and cell proliferation), and several osteogenic pathways (MAPK signaling pathway, TGF-?/BMP signaling pathway, and Wnt signaling pathway). Finally, TGF-?/BMP signaling pathway was selected for target verification and function analysis. We observed that a number of osteo-genes in the TGF-?/BMP superfamily, such as BMPRI, BMPRII, TGFBRI, TGFBRII, BMP4, TGF?, Smad2, 3, 8, were predicted to be target gene of the differentially expressed miRNAs. Among them, TGFB, BMP4, BMPRI, and Smad8, which are positive regulators in osteoblast differentiation, were confirmed to be significantly up-regulated in VD3-induced cells by qRT-PCR; while Smad6 and activinRI, which are negative regulators of the TGF-?/BMP superfamily, were shown to be significantly down-regulated. These results will help to understand the role of miRNA in the regulation of the osteogenic differentiation of hAMSCs.

SUBMITTER: Gu H

PROVIDER: S-EPMC5714771 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Identification and differential expression of microRNAs in 1, 25-dihydroxyvitamin D3-induced osteogenic differentiation of human adipose-derived mesenchymal stem cells.

Gu Huijie H Xu Jun J Huang Zhongyue Z Wu Liang L Zhou Kaifeng K Zhang Yiming Y Chen Jiong J Xia Jiangni J Yin Xiaofan X

American journal of translational research 20171115 11

The aim of this study was to identify specific microRNAs (miRNAs) and their regulatory roles in the process of 1, 25-dihydroxyvitamin D3-induced (VD3-induced) osteogenic differentiation of human adipose-derived Mesenchymal stem cells (hAMSCs). The differentially expressed miRNAs in VD3-induced hAMSCs was examined. The putative target genes of these miRNAs were predicted. A total of 76 conserved miRNAs, including 18 miRNAs were significantly up-regulated and 58 miRNAs were significantly downregul ...[more]

PMID: 29218085

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Project description:We previously demonstrated that non-small cell lung cancer (NSCLC) cells and primary human lung tumors aberrantly express the vitamin D3-catabolizing enzyme, CYP24, and that CYP24 restricts transcriptional regulation and growth control by 1?,25-dihydroxyvitamin D3 (1,25(OH)2D3) in NSCLC cells. To ascertain the basis for CYP24 dysregulation, we assembled a panel of cell lines that represent distinct molecular classes of lung cancer: cell lines were selected which harbored mutually exclusive mutations in either the K-ras or the Epidermal Growth Factor Receptor (EGFR) genes. We observed that K-ras mutant lines displayed a basal vitamin D receptor (VDR)(low)CYP24(high) phenotype, whereas EGFR mutant lines had a VDR(high)CYP24(low) phenotype. A mutation-associated difference in CYP24 expression was also observed in clinical specimens. Specifically, K-ras mutation was associated with a median 4.2-fold increase in CYP24 mRNA expression (p=4.8×10(-7)) compared to EGFR mutation in a series of 147 primary lung adenocarcinoma cases. Because of their differential basal expression of VDR and CYP24, we hypothesized that NSCLC cells with an EGFR mutation would be more responsive to 1,25(OH)2D3 treatment than those with a K-ras mutation. To test this, we measured the ability of 1,25(OH)2D3 to increase reporter gene activity, induce transcription of endogenous target genes, and suppress colony formation. In each assay, the extent of 1,25(OH)2D3 response was greater in EGFR mutation-positive HCC827 and H1975 cells than in K-ras mutation-positive A549 and 128.88T cells. We subsequently examined the effect of combining 1,25(OH)2D3 with erlotinib, which is used clinically in the treatment of EGFR mutation-positive NSCLC. 1,25(OH)2D3/erlotinib combination resulted in significantly greater growth inhibition than either single agent in both the erlotinib-sensitive HCC827 cell line and the erlotinib-resistant H1975 cell line. These data are the first to suggest that EGFR mutations may identify a lung cancer subset which remains responsive to and is likely to benefit from 1,25(OH)2D3 administration. This article is part of a Special Issue entitled 'Vitamin D Workshop'.

Project description:Background and objectivesElevated concentrations of fibroblast growth factor 23 (FGF23) are postulated to promote 25-hydroxyvitamin D (25[OH]D) insufficiency in CKD by stimulating 24-hydroxylation of this metabolite, leading to its subsequent degradation; however, prospective human studies testing this relationship are lacking.Design, setting, participants, & measurementsAn open-label prospective study was conducted from October 2010 through July 2012 to compare the effect of 8 weeks of oral cholecalciferol therapy (50,000 IU twice weekly) on the production of 24,25(OH)2D3 in vitamin D-insufficient patients with CKD (n=15) and controls with normal kidney function (n=15). Vitamin D metabolites were comprehensively profiled at baseline and after treatment, along with FGF23 and other mineral metabolism parameters.ResultsVitamin D3 and 25(OH)D3 concentrations increased equivalently in the CKD and control groups following cholecalciferol treatment (median D3 change, 8.6 ng/ml [interquartile range, 3.9-25.6 ng/ml] for controls versus 12.6 ng/ml [6.9-41.2 ng/ml] for CKD [P=0.15]; 25(OH)D3 change, 39.2 ng/ml [30.9-47.2 ng/ml] for controls versus 39.9 ng/ml [31.5-44.1 ng/ml] for CKD [P=0.58]). Likewise, the absolute increase in 1α,25(OH)2D3 was similar between CKD participants and controls (change, 111.2 pg/ml [64.3-141.6 pg/ml] for controls versus 101.1 pg/ml [74.2-123.1 pg/ml] for CKD; P=0.38). Baseline and post-treatment 24,25(OH)2D3 concentrations were lower in the CKD group; moreover, the absolute increase in 24,25(OH)2D3 after therapy was markedly smaller in patients with CKD (change, 2.8 ng/ml [2.3-3.5 ng/ml] for controls versus 1.2 ng/ml [0.6-1.9 ng/ml] for patients with CKD; P<0.001). Furthermore, higher baseline FGF23 concentrations were associated with smaller increments in 24,25(OH)2D3 for individuals with CKD; this association was negated after adjustment for eGFR by multivariate analysis.ConclusionsPatients with CKD exhibit an altered ability to increase serum 24,25(OH)2D3 after cholecalciferol therapy, suggesting decreased 24-hydroxylase activity in CKD. The observed relationship between baseline FGF23 and increments in 24,25(OH)2D3 further refutes the idea that FGF23 directly contributes to 25(OH)D insufficiency in CKD through stimulation of 24-hydroxylase activity.

Dataset Information

Identification and differential expression of microRNAs in 1, 25-dihydroxyvitamin D3-induced osteogenic differentiation of human adipose-derived mesenchymal stem cells.

Publications

Identification and differential expression of microRNAs in 1, 25-dihydroxyvitamin D3-induced osteogenic differentiation of human adipose-derived mesenchymal stem cells.

Similar Datasets

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