Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glioma remains one of the most lethal human tumors in spite of the progress in radiotherapy, chemotherapy, and surgical techniques. Cell differentiation agent-2 (CDA-2) is an extraction from healthy human urine consisting of primary organic acids and peptides, and it has been demonstrated to inhibit growth and induce differentiation in glioma and other cell lines. However, the mechanism remains unclear. Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptors (NHRs) which are involved in cellular differentiation and proliferation. In this study, we investigated if CDA-2 induced differentiation of SWO-38 glioma cells is mediated by PPARgamma. CDA-2 induced differentiation of SWO-38 cells was characterized by typical morphological changes, increased expression of GFAP, inhibition of proliferation and G(0)/G(1) cell cycle arrest. CDA-2 also triggered up-regulation of PPARgamma, GFAP and PTEN protein and a reduction of COX-2 protein. However, the effects of CDA-2 on SWO-38 cells could be partly reversed by GW9662, an irreversible PPARgamma antagonist. Our investigation demonstrated that CDA-2 could be a potential drug for tumor differentiation therapy, and activation of the PPARgamma pathway might be a crucial factor in glioma differentiation induced by CDA-2.
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PMID:Differentiation of SWO-38 glioma cells induced by CDA-2 is mediated by peroxisome proliferator-activated receptor gamma. 1943 72

Cell differentiation agent-2 (CDA-2) is an extraction from healthy human urine consisting of primary organic acids and peptides, and it has been demonstrated to inhibit growth and induce differentiation in glioma and other cell lines. But the mechanism of CDA-2 remains unclear. In this study, we demonstrated that CDA-2 inhibited cell growth and induced differentiation of glioma cells, accompanied with decreased expression of SLUG, Twist and Vimentin in both SWO-38 and U251 cell lines. Overexpression of SLUG or Twist greatly eliminated the efficiency of CDA-2 in inducing differentiation. Further study showed that CDA-2 treatment resulted in great changed microRNAs (miRNAs) detected by quantitative PCR, in which miR-124 was one of the most changed miRNAs and its level was increased by fourfold. The result of miRNA target prediction showed that miR-124 could regulate hundreds of genes which were relative to cell differentiation, such as SLUG, Vimentin, actin cytoskeleton, focal adhesion, tight junction. Inhibition of miR-124 up-regulated SLUG, Twist and Vimentin proteins, and partly eliminated the function of CDA-2 on these mesenchymal markers. Our findings demonstrated for the first time that CDA-2 induced cell differentiation through suppressing Twist and SLUG via miR-124 in glioma cells.
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PMID:CDA-2 induces cell differentiation through suppressing Twist/SLUG signaling via miR-124 in glioma. 2291 90

The aberrant expression of cyclin-dependent kinase-4 (CDK4) has previously been observed in human brain glioma. Furthermore, it is observed that up-regulation of CDK4 is associated with therapy resistance and relapse. However, the mechanisms behind these phenomena remain unclear. Here, we demonstrated that elevated CDK4 expression is correlated with poor prognosis in glioma after radiotherapy and that CDK4 knockdown conferred radiosensitivity in glioma cell lines. CDK4 was identified as potential downstream target of miR-124 through bioinformatics analysis and dual-firefly luciferase reporter assay. Furthermore, restoration of miR-124 could confer radiosensitivity. Cell differentiation agent-2 (CDA-2) mimicked the effect of miR-124 restoration and CDK4 knockdown, and sensitized xenografts to radiation in an animal model. Our findings demonstrated for the first time that CDK4 was a downstream target of miR-124 and that CDA-2 could radiosensitize Glioblastoma multiforme cells through the MiR-124-CDK4 axis.
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PMID:miR-124 radiosensitizes human glioma cells by targeting CDK4. 2376 Oct 23