Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.1.1.37 (DNA methyltransferase)
 4,983 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chronic lymphocytic leukemia (CLL) is the most common leukemia in Western countries. In CLL, a large number of genes affecting cancer-related pathways may be dysregulated by epigenetic silencing. We analysed by methylation-specific polymerase chain reaction the CpG island methylation status of 15 well-characterised cancer-related genes in 32 patients with CLL. Aberrant methylation in the sample of patients with CLL was shown for secreted frizzled-related protein 1 (68.8%), secreted frizzled-related protein 2 (65.6%), death-associated protein kinase 1 (50.0%), E-cadherin (21.9%), secreted frizzled-related protein 4 (15.6%), p15 (9.4%), p16 (6.3%), retinoic acid receptor beta2 (3.1%), secreted frizzled-related protein 5 (3.1%) and tissue inhibitor of matrix metalloproteinases 3 (3.1%). For human Mut-L homolog 1, O(6)-methylguanine DNA methyltransferase, p73, suppressor of cytokine signalling 1 and tissue inhibitor of matrix metalloproteinases 2 no hypermethylation was detected. Hypermethylation of at least one gene was observed in 87.5% of the samples. Our results show that aberrant CpG island methylation affecting cancer-related pathways such as Wnt signalling, regulation of apoptosis, cell cycle control and tissue invasion is a common phenomenon in CLL. Epigenetic disturbances may be involved in the pathogenesis of CLL and thus may provide a molecular rationale for therapeutic approaches.
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PMID:CpG island methylation patterns in chronic lymphocytic leukemia. 1934 29

Rheumatoid arthritis (RA) is an autoimmune and progressive systemic disease of unknown etiology. Research shows that fibroblast-like synoviocytes (FLS) participate in the cartilage erosion, synovial hyperplasia, inflammatory cytokine secretion and suggests that fibroblast-like synoviocytes (FLS) display a crucial role in RA pathogenesis. Recent studies have suggested the role of the Wnt signaling pathway in the pathogenesis of RA. In previous study, we identified that increased methyl-CpG-binding protein 2 (MeCP2) reduced the secreted frizzled-related protein 4 (SFRP4) expression in FLS in Arthritic rat model and the DNA methyltransferase (DNMT) inhibitor 5-Aza-2'-deoxycytidine (5-azadC) could induce the SFRP4 expression, indicating that DNMT has a key role in the differential expression of SFRP4. MicroRNAs (MiRNAs), which are small non-coding RNAs, are involved in diverse biological functions, regulation of gene expression, pathogenesis of autoimmune disease and carcinogenesis. In light of the directly down-regulation of miR-152 on DNMT1 expression by targeting the 3' untranslated regions of its transcript in nickel sulfide (NiS)-transformed human bronchial epithelial cells, we investigated whether miR-152 is aberrantly expressed and targets DNMT1 in FLS in Arthritic rat model. Our results demonstrated that the expression of miR-152 was specifically down-regulated in Arthritic rat model, whereas up-regulation of miR-152 in FLS resulted in a marked reduction of DNMT1 expression. Further experiments revealed that increased miR-152 indirectly up-regulated the SFRP4 expression, a negative regulator of WNT signaling pathway, by targeting the DNMT1. Moreover, activation of miR-152 expression in FLS could inhibit the canonical Wnt pathway activation and result in a significant decrease of FLS proliferation. MiR-152 and DNA methylation may provide molecular mechanisms for the activation of canonical Wnt pathway in RA. Combination of miR-152 and DNMT1 may be a promising treatment strategy for RA patients in which SFRP4 is inactivated.
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PMID:MicroRNA-152 modulates the canonical Wnt pathway activation by targeting DNA methyltransferase 1 in arthritic rat model. 2519 84