Ugonin inhibits chondrosarcoma metastasis through suppressing cathepsin V via promoting miR-4799-5p expression
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ABSTRACT:
PROVIDER: PRJNA1175665 | ENA |
REPOSITORIES: ENA
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Project description:Chondrosarcoma is a rare type of bone cancer that develops in cartilage cells. Ugonin V is a flavonoid compound that has been extracted from the plant Helminthostachys zeylanica (L.) Hook. This study examined the molecular therapeutic effects of ugonin V on chondrosarcoma metastasis.
2024-10-23 | GSE279984 | GEO
Project description:microRNA-7-5p (miR-7-5p) is an established tumor suppressor in multiple cancer types and inhibits growth and invasion by suppressing expression and activity of the epidermal growth factor receptor (EGFR) signaling pathway. While melanoma is not typically driven by EGFR signaling, expression of miR-7-5p is reduced in metastatic tumors compared to primary melanoma. Here, we investigated the biological and clinical significance of miR-7-5p in melanoma. Our results showed that augmenting miR-7-5p expression in vitro markedly reduced tumor cell viability, colony formation and induced cell cycle arrest. Furthermore, ectopic expression of miR-7-5p reduced migration and invasion of melanoma cells in vitro and reduced melanoma lung colonizationmetastasis in vivo. To investigate the mechanism underlying this effect, we used cDNA microarray analysis to identify a subset of putative miR-7-5p target genes associated with melanoma and metastasis. Of these, we confirmed nuclear factor kappa B (NF-κB) subunit RelA, as a novel direct target of miR-7-5p in melanoma cells, such that miR-7-5p suppresses NF-κB activity to decrease expression of canonical NF-κB target genes, including IL-1a, IL-6 and IL-8. Importantly, the effects of miR-7-5p on melanoma cell growth, cell cycle, migration and invasion were recapitulated by RelA knockdown. Finally, analysis of gene array datasets from multiple melanoma patient cohorts revealed an association between elevated RelA expression and poor survival, further emphasizing the clinical significance of RelA and its downstream signaling effectors.. Taken together, our data suggest that miR-7-5p replacement therapy might have clinical utility in melanoma to inhibit the metastatic process, in part through its inactivation of RelA/NF-kB signaling. Total RNA was extracted from WM266-4 cells transfected with miR-NC or miR-7-5p precursor molecules (30 nM) for 24 h, using Qiazol reagent (Qiagen).
2016-02-10 | E-GEOD-77196 | biostudies-arrayexpress
Project description:microRNA-7-5p (miR-7-5p) is an established tumor suppressor in multiple cancer types and inhibits growth and invasion by suppressing expression and activity of the epidermal growth factor receptor (EGFR) signaling pathway. While melanoma is not typically driven by EGFR signaling, expression of miR-7-5p is reduced in metastatic tumors compared to primary melanoma. Here, we investigated the biological and clinical significance of miR-7-5p in melanoma. Our results showed that augmenting miR-7-5p expression in vitro markedly reduced tumor cell viability, colony formation and induced cell cycle arrest. Furthermore, ectopic expression of miR-7-5p reduced migration and invasion of melanoma cells in vitro and reduced melanoma lung colonizationmetastasis in vivo. To investigate the mechanism underlying this effect, we used cDNA microarray analysis to identify a subset of putative miR-7-5p target genes associated with melanoma and metastasis. Of these, we confirmed nuclear factor kappa B (NF-κB) subunit RelA, as a novel direct target of miR-7-5p in melanoma cells, such that miR-7-5p suppresses NF-κB activity to decrease expression of canonical NF-κB target genes, including IL-1a, IL-6 and IL-8. Importantly, the effects of miR-7-5p on melanoma cell growth, cell cycle, migration and invasion were recapitulated by RelA knockdown. Finally, analysis of gene array datasets from multiple melanoma patient cohorts revealed an association between elevated RelA expression and poor survival, further emphasizing the clinical significance of RelA and its downstream signaling effectors.. Taken together, our data suggest that miR-7-5p replacement therapy might have clinical utility in melanoma to inhibit the metastatic process, in part through its inactivation of RelA/NF-kB signaling.
2016-02-10 | GSE77196 | GEO
Project description:Mice bearing primary human chondrosarcoma xenografts were treated with IPI 926, and mRNA levels of known Hh pathway genes and endpoint tumor volumes were measured. Gene expression profiling of IPI-926 treated tumors was conducted to identify potential novel Hh target genes. 4 Control treated and 4 IPI-926 treated NSG Mice. Primary tumor was obtained from a single chondrosarcoma patient.
2014-03-18 | E-GEOD-44581 | biostudies-arrayexpress
Project description:Transcriptional profiling of human chondrosarcoma sphere vs adherent cells
2015-04-30 | GSE47823 | GEO
Project description:These libraries represent instances of Swarm rat chondrosarcoma tumors taken from different transplantation experiments. This series also contains one non-cancerous cartilage library made from rat normal growing femoral head cartilage as a comparative data point. Keywords: other
2004-07-24 | GSE1517 | GEO
Project description:Mice bearing primary human chondrosarcoma xenografts were treated with IPI 926, and mRNA levels of known Hh pathway genes and endpoint tumor volumes were measured. Gene expression profiling of IPI-926 treated tumors was conducted to identify potential novel Hh target genes.
2014-03-18 | GSE44581 | GEO
Project description:Cathepsin L is a lysosomal protease that is secreted by several cancer cells. Cathepsin L upregulation has been widely associated with poor clinical outcome and increased metastatic incidence. However, whether Cathepsin L participates in tumor angiogenesis remains less studied. Our study showed a significant activation of angiogenic capacity of endothelial cells in presence of purified or tumor derived Cathepsin L. In addition, Cathepsin L exposure led to a significant increase in the proliferative capacity of endothelial cells. While the ability of Cathepsin L to promote endothelial cell sprouting, migration, invasion and tube formation can be attributed to its proteolytic effects on extracellular matrix, how it promotes endothelial cell proliferation remains obscure. The objective of this study was to test if Cathepsin L exposure can activate signaling cascades and gene expression leading to proliferation of endothelial cells.
2016-06-20 | GSE75744 | GEO
Project description:The goal of this study was comparative analysis of differentially expressed miRNA and their targets in human chondrosarcoma JJ012 not treated (Control) and JJ012 chondrosarcoma cell line treated with antitumorigenic neuropeptide PRP-1. The goal was to elucidate the major signal transduction pathways deregulation in sarcomagenesis. Total RNA extraction was followed by the analysis of RNA quality and integrity, Exiqon human miRNA panel of 743 unique miRNA assays,was performed. performed.211 unique gene targets were detected for downregulated miRNAs and 104 unique target genes for upregulated miRNAs with 28 target genes common for both. out of 122 upregulated and 109 downregulated , total 9 differentially statistically significant miRNAs(3 upregulated and 6 downregulated) fitting P<0.05 by Benjamini Hochberg were detected when comparing chondrosarcoma cell line treted to not treated control using human Exiqon arrays with biological triplicates.: miR192, regulating cell cycle checkpoinrts was upregulated in treated samples 4 fold, miR125b, known as tumor suppressor in sarcomas was upregulated 4.87 fold. miR20a was upregulated 5.29 , known to form complexes with Argonaute proteins-part of RNA induced silencing complex (RISC) Downregulated miRNas included miR509-3p (12.88 fold), its targets Yap, Rac1 and Yes1 known to be associated with Src kinase activity; miR589 was downregulated 7.46 fold , targets Src adaptors'. miR 302c was downregulated6.46 fold and miR199a=5p -5.66 fold , that acted as oncogenes in sarcomas. miR584 involved on cell migration and TGFbeta signaling was downregulated 4.78 fold Comparison of miRNA expression between control samples and samples treated with antiproliferative cytostatic mTORC1 inhibitor PRP-1 cytokine in human chondrosarcoma JJ012 cell line
2013-10-31 | E-GEOD-49545 | biostudies-arrayexpress
Project description:Chondrosarcoma is the second most common type of bone cancer. At present, the most effective clinical course of action is surgical resection. Cisplatin is the chemotherapeutic medication most widely used for the treatment of chondrosarcoma; however, its effectiveness is severely hampered by drug resistance. In the current study, we compared cisplatin-resistant chondrosarcoma SW1353 cells with their parental cells via RNA sequencing. Our analysis revealed that glutamine metabolism is highly activated in resistant cells but glucose metabolism is not. Amphiregulin (AR), a ligand of the epidermal growth factor receptor, enhances glutamine metabolism and supports cisplatin resistance in human chondrosarcoma by promoting NADPH production and inhibiting ROS accumulation. The MEK, ERK, and NrF2 signaling pathways were shown to regulate AR-mediated SLC1A5 and GLS expression as well as glutamine metabolism in cisplatin-resistant chondrosarcoma. The knockdown of AR expression in cisplatin-resistant chondrosarcoma cells was shown to reduce the expression of SLC1A5 and GLS in vivo. These results indicate that AR and glutamine metabolism are worth pursuing as therapeutic targets in dealing with cisplatin-resistant human chondrosarcoma.
2023-08-07 | GSE239911 | GEO