In summary, we present the first comprehensive proteomic analysis of the widely studied Dnmt1 hypomorph colorectal cancer cells and identify redistribution of Dnmt1 and its interaction partner Beta-Catenin.
In this study we report synergistic antitumor activity of Laccaic acid (LA) and Phenethyl isothiocyanate (PEITC) combination in colorectal cancer via dual inhibition of DNA methyltransferase-1 and Histone deacetylase-1.
The potential role of methylation and histone acetylation in the regulation of miR-32 expression in CRC cells was investigated using the demethylation reagent 5-aza-2'-deoxycytidine (5-Aza-dC), the histone deacetylase inhibitor trichostatin A (TSA) and transfection of DNA methyltransferase 1 (DNMT1) overexpression plasmid.
CuB significantly increased BTG3 levels, induced promoter demethylation, and decreased the levels of DNA methyltransferases (DNMT1, DNMT3a and DNMT3b) in both CRC cell lines (SW480 and Caco-2), and the effects of CuB were comparable with those of 5-Aza-dC.
In conclusion, our data showed that miR-124 and miR-506 inhibit progression and increase sensitivity to chemotherapy by targeting DNMT3B and DNMT1 in CRC.
We conclude from these results that targeting calpain, UHRF1, and DNMT1 using luteolin could be an interesting way to prevent and/or treat colorectal cancers.
In conclusion, it was demonstrated that IL-23, assisted by STAT5, might only promote the metastasis of CRC with deficient Socs3 expression in which IL-23-induced DNMT-1 was involved.
Based on these observations, we conclude that chemotherapy and radiotherapy inhibit DNMT1 expression to upregulate BNIP3 expression to promote CRC cell apoptosis.
Promoter methylation of the p14(ARF) gene and messenger RNA (mRNA) expression levels of p14(ARF), DNA methyltransferase 1 (DNMT1), and DNMT3b were investigated by using methylation-specific polymerase chain reaction (PCR) analysis (MSP) and quantitative real-time PCR analysis in fresh tissues from 188 patients with colorectal cancer.
These findings suggested that DNMT1 was associated with the malignant phenotype, and dysregulation of DNMT1 expression was present in tumor cells of CRC.
Mutations in coding exons of the DNMT1 gene were detected in two (7%) of the colorectal cancers: they consisted of one-base deletion resulting in deletion of the whole catalytic domain and a point mutation resulting in a single amino acid substitution.
The fidelity of DNMT1 expression was further undermined in colorectal carcinomas, in which a striking heterogeneity in DNMT1 expression, with some carcinoma cells containing very high DNMT1 levels and others containing very low DNMT1 levels, was observed.