Project description:Invastigation of whole genome gene expression level changes in human osteosarcoma cell line MNNG/HOS sarcospheres,hypoxia-induced sarcospheres and TGF-beta1 induced sarcospheres. A three chip study using total RNA cover from three cultures of human osteosarcoma cell line MNNG/HOS sarcospheres, hypoxia-induced sarcospheres and TGF-beta1-induced sarcospheres. Each chip measures the expression level of 45033 genes from osteosarcoma cell line MNNG/HOS.
Project description:This SuperSeries is composed of the following subset Series: GSE38133: TGF-beta1 effect on human osteosarcoma cell line MNNG/HOS GSE38134: Expression analysis of human osteosarcoma cell line MNNG/HOS sarcospheres, hypoxia-induced sarcospheres and TGF-beta1-induced sarcospheres Refer to individual Series
Project description:Invastigation of whole genome gene expression level changes in human osteosarcoma cell line MNNG/HOS sarcospheres,hypoxia-induced sarcospheres and TGF-beta1 induced sarcospheres.
Project description:Investigation of whole genome gene expression level changes in human osteosarcoma cell line MNNG/HOS treated by TGF-beta1 for three days (mesophase) and five days (sarcospheres iOSCs), compared to non-treatment cells (residual adherent cells). A three chip study using total RNA cover from three cultures of non-treatment human osteosarcoma cell line MNNG/HOS (residual adherent cells), TGF-beta1 treated three days osteosarcoma cell line MNNG/HOS (mesophase) and TGF-beta1 treated five days osteosarcoma cell line MNNG/HOS ( only collected the suspending sarcospheres iOSCs). Each chip measures the expression level of 45033 genes from osteosarcoma cell line MNNG/HOS.
Project description:Investigation of whole genome gene expression level changes in human osteosarcoma cell line MNNG/HOS treated by TGF-beta1 for three days (mesophase) and five days (sarcospheres iOSCs), compared to non-treatment cells (residual adherent cells).
Project description:Due to the lack of a precise in vitro model that can mimic the nature microenvironment in osteosarcoma, the understanding of its resistance to chemical drugs remains limited. Here, we report a novel three-dimensional model of osteosarcoma constructed by seeding tumor cells (MG-63 and MNNG/HOS Cl #5) within in demineralized bone matrix scaffolds. Demineralized bone matrix scaffolds retain the original components of the natural bone matrix (hydroxyapatite and collagen type I), and possess good biocompatibility allowing osteosarcoma cells to proliferate and aggregate into clusters within the pores. Growing within the scaffold conferred elevated resistance to doxorubicin on MG-63 and MNNG/HOS Cl #5 cell lines as compared with two-dimensional cultures. Transcriptomic analysis showed an increased enrichment for drug resistance genes along with enhanced glutamine metabolism in osteosarcoma cells in demineralized bone matrix scaffolds. Inhibition of glutamine metabolism resulted a decrease in drug resistance of osteosarcoma, which could be restored by α-ketoglutarate supplementation. Overall, our study suggests that microenvironmental cues in demineralized bone matrix scaffolds can enhance osteosarcoma drug responses and that targeting glutamine metabolism may be a strategy for treating osteosarcoma drug resistance.
Project description:Analysis of genes induced by TGF-beta1 in human lung fibroblasts. TGF-beta1 is essential for fibroblast -myofibroblast differentiation, which is a hallmark in the development of lung fibrosis. Newly identified genes up- or down-regulated by TGF-beta1 in human lung fibroblasts may serve as pharmacological target for therapeutic options in patients with lung fibrosis.
Project description:Bromodomain and extra terminal domain (BET) proteins are important epigenetic regulators facilitating the transcription of genes in chromatin areas linked to acetylated histones. JQ1, a BET protein inhibitor, has antiproliferative activity against many cancers, mainly through inhibition of c-MYC and upregulation of p21. In this research, we investigated the use of JQ1 for human osteosarcoma (OS) treatment. JQ1 significantly inhibited the proliferation and survival of OS cells inducing G1 cell cycle arrest, premature senescence, but little effect on apoptosis. Interestingly, c-MYC protein levels in JQ1-treated cells remained unchanged, whereas the upregulation of p21 protein was still observable. Although effective in vitro, JQ1 alone failed to reduce the size of the MNNG/HOS xenografts in immunocompromised mice. To overcome the resistance of OS cells to JQ1 treatment, we combined JQ1 with rapamycin, an mTOR inhibitor. JQ1 and rapamycin synergistically inhibited the growth and survival of OS cells in vitro and in vivo. We also identified that RUNX2 is a direct target of BRD4 inhibition by JQ1 in OS cells. Chromatin immunoprecipitation (ChIP) showed that enrichment of BRD4 protein around RUNX2 transcription start sites diminished with JQ1 treatment in MNNG/HOS cells. Overexpression of RUNX2 protected JQ1-sensitive OS cells from the effect of JQ1, and siRNA-mediated inhibition of RUNX2 sensitized the same cells to JQ1. In conclusion, our findings suggest that JQ1, in combination with rapamycin, is an effective chemotherapeutic option for OS treatment. We also show that inhibition of RUNX2 expression by JQ1 partly explains antiproliferative activity of JQ1 in OS cells. MNNG/HOS cells treated with 7.5mM JQ1, 12.5nM Rapamycin or both were used for RNA extraction and hybridization on Affymetrix microarrays. We compared these microarray samples with the corresponding control (treated with DMSO).