Project description:To elucidate whether ZFP90 plays a role in colorectal cancer tumorigenesis, a RNA-seq analysis was performed to compare the gene expression profiles of ZFP90-KO and control Control cell.
Project description:Chronic inflammation and gut microbiota dysbiosis are risk factors for colorectal cancer. In clinical practice, inflammatory bowel disease (IBD) patients have a greatly increased risk of developing colitis associated colorectal cancer (CAC). However, the basis underlying the initiation of CAC remains to be explored. Systematic filtration through existing genome-wide association study (GWAS) and conditional deletion of Zfp90 in CAC mice model indicated that Zfp90 was a putative oncogene in CAC development. Strikingly, depletion of gut microbiota eliminated the tumorigenic effect of Zfp90 in CAC mice model. Moreover, fecal microbiota transplantation demonstrated Zfp90 promoted CAC depending on gut microbiota. Combining 16s rDNA sequencing in feces specimens from CAC mice model, we speculated that Prevotella copri-defined microbiota might mediate the oncogenic role of Zfp90 in the development of CAC. Mechanistic studies revealed Zfp90 accelerated CAC development through Tlr4-Pi3k-Akt-Nf-κb pathway. Our findings elucidated the crucial role of Zfp90-microbiota-Nf-κb axis in creating a tumor-promoting environment and suggested therapeutic targets for CAC prevention and treatment.
Project description:Previous reports have indicated that RNA m6A modification plays an important role in colorectal carcinogenesis. We hypothesized that F. nucleatum promoted colorectal carcinogenesis dependent on RNA m6A alterations. To test this hypothesis, we conducted a RNA-seq analysis in HT29 cells cocultured with F. nucleatum and medium control.
Project description:ChREBP is a glucose-responsive transcription factor involved in glycolysis and de novo lipogenesis. Elevated ChREBP levels were observed in human colorectal cancer (CRC) samples and correlated with poor 5-year survival rates in patients. To investigate the role and mechanism of ChREBP in colorectal carcinogenesis in vivo, we used ChREBP knockout mice, which were intraperitoneally injected with azoxymethane (AOM) followed by dextran sulfate sodium (DSS) in drinking water. In the AOM/DSS-induced colorectal cancer model, carcinogenesis was reduced in ChREBP null mice. In the initial phases of colorectal carcinogenesis, ChREBP deficiency was associated with diminished epithelial cell proliferation and a lower number of aberrant crypt foci (ACF), but it had no impact on DNA damage or the severity of colitis. The key transcription factor beta-catenin and Wnt target gene expression were both decreased in the colons of ChREBP null mice and in ChREBP-knockdown Caco-2 colorectal cancer cells. In vitro studies showed that ChREBP knockdown promoted beta-catenin phosphorylation and reduced beta-catenin levels and nuclear localization in Caco-2 cells. Conversely, ChREBP overexpression was sufficient to promote beta-catenin accumulation, nuclear localization, and transcriptional activity in human HEK293T cells, thereby contributing to compensatory proliferation and tumorigenesis. Given its elevated expression in human colorectal cancer, ChREBP may represent a potential therapeutic target. The correlation between ChREBP-mediated Wnt signaling activation and colorectal carcinogenesis would provide deeper insights into the link between metabolic dysfunction and colorectal cancer.