<b>Conclusions:</b> These results indicate that G9a-induced and p53-dependent epigenetic programing stimulates the growth of colon cancer, which also suggests that G9a inhibitors that restore p53 activity are promising therapeutic agents for treating colon cancer, especially for CRC expressing wild-type p53.
A point mutation at codon 12 of the K-ras gene was found, while no alterations were noted in the p53 gene, whose mutations are frequent in colon cancers.
A recent study reported that a point mutation (G/T) in the p53 binding sequence in a colon cancer cell line completely impaired p53R2 protein activity.
Also, the method was applied to the assay of p53 in human plasma sample and normal and malignant cell line lysates such as (L929 normal cell Line from mouse C3H (L929), colon cancer cell-HCT, prostate cancer cell line PC-3, and human breast adenocarcinoma cell line-MCF7).
Although the significance of this observation with respect to carcinogenesis remains to be established, the data suggest that ING1L might be involved in colon cancers through interference with signal(s) transmitted through p53 and p33(ING1).
Altogether, targeting BNIP3L in wild-type p53colon cancer cells is a novel anticancer strategy activating iron depletion signaling and the mitophagy-related cell death pathway.
Analytical scanning of the p53 gene by FAMA in DNA from colon cancer samples provides a sensitive, accurate and specific diagnostic procedure for routine clinical application.
As loss of p53 in colon cancer cells contributes to resistance against anticancer drugs, and thus to reoccurrence of colon cancer, targeted delivery of silica NPs could be envisioned to also deplete p53 deficient tumor cells.
By array analysis, there were 17 significantly down-regulated and 7 significantly up-regulated miRNAs in subjects who later developed neoplasia. miR-215 was significantly up-regulated both 1-2 years prior to the onset of neoplasia (3.5-fold, <i>p</i> < 0.001) and 3-5 years prior to the onset of neoplasia (5.4-fold, <i>p</i> = 0.007). miR-215 expression was also increased in UC-associated colon cancers (5.3-fold, <i>p</i> = 0.03) and adjacent non-dysplastic UC tissue (6.2-fold, <i>p</i> = 0.02). p53 was expressed in 20% of patients prior to the onset of neoplasia and in 67% of UC-associated colon cancers, although was not correlated with miR-215 expression.
By using pairs of isogenic colon cancer cell lines that differ only in p53 expression (RKO and HCT116), securinine was found to exhibit these properties.
c-FLIP is specially overexpressed in colon cancers and it might contribute to carcinogenesis of normal colonic mucosa. p53 may exert transcriptional upregulation effects on c-FLIP gene and more potent effects on promoting the degradation of c-FLIP protein.
Clonogenic survival analyses were performed using the human colon cancer cell lines HCT 116 wt and the isogenic p53 deficient cell line HCT 116 p53 -/-.
Collectively, our findings present the first to elucidate that miR-29c is a direct p53 target gene, and also identify PHLDB2 as an important miR-29c target gene involved in colon cancer metastasis.
Cytotoxicity assays showed that Adp14 had a statistically significantly (P =.002) greater effect on colon cancer (HCT116) cell lines containing two copies of the wild-type p53 gene than on p53-null cells, suggesting that functional p53 is a critical determinant of p14(ARF)-mediated cytotoxicity.
Data analysis comparing colon cancer entries in the TP53 database (http://p53.curie.fr) with the results reported in this study showed that distribution of mutations and the mutational events were comparable.