Nat Commun: The occurrence of intestinal cancer and the maintenance of tumor stem driven by the metastatic genetic regulatory factor Mll1 mediated the Wnt path

Previous studies have shown that the Wnt/β-catenin signal transducting path path can regulate the self-renewal of adult stem cells and promote tumor development.
-activated Wnt/β-catenin signal transducting path is shown to be associated with colon cancer and many other cancers.
Invigoration of a destructive compound consisting of APC, Gsk3 beta, and Axin1/2 improves the stability of β-catenin, without which β-catenin is phosphatized and ubigenized, and eventually degraded by protease.
growing evidence that the Wnt/β-catenin signal transducting path is critical to the development of bowel cancer and the maintenance of bowel cancer stem cells.
the associated gene mutations in this path line can induce bowel cancer by promoting the stability and excessive activation of β-catenin abnormalities.
study, researchers identified histone methyl transferase Mll1 as a regulatory factor in the development of bowel cancer driven by the Wnt path.
researchers found that Mll1 was highly expressed in Lgr5 plus stem cells β-catenin expression elevated in human colon cancer tissue.
high expression levels of MLL1 were associated with poor prognostication in colon cancer patients.
the Mll1 high expression Mll1 gene knockout mouse model in colon cancer and Lgr5 plus intestinal stem cells can effectively prevent the production of wnt/β-catenin-driven adenomas caused by Lgr5 plus intestinal stem cells.
knock-out of Mll1 can reduce the self-renewal of human colon cancer tumor ococytes and inhibit the growth of transplant tumors.
further studies have shown that Mll1 regulates the expression levels of stem cell-related genes, including the Wnt/β-catenin target gene Lgr5.
In the absence of Mll1, the myoglobin methylation modification in the stem cell promoter region changed from the activated H3K4 trimethylation state to the inhibitory H3K27 trimethylation state, indicating that Mll1 was able to maintain the expression of stem cell-related genes through the H3K27 trimethylation gene silencing mechanism mediated by antagonizing PRC2.
histological analysis of the starting cells of intestinal tumors carrying Wnt mutations showed that Mll1 was able to regulate the expression of Gata4/6 transcription factors, which maintain the dryness of cancer cells and regulate the differentiation of cup cells.
Mll1 regulates the expression of stem cell-related genes through supergeogenetics, and the results show that Mll1 is an important factor in the occurrence of intestinal tumors mediated by the Wnt/β-catenin pathogenesiary and the maintenance of tumor stem cell characteristics.
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