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:Colorectal cancer is a chronic inflammation-associated tumor and the immune system, besides protecting the host from developing tumors, can support the CRC progression. In this scenario, due to its capability to elicit the production of cytokines, gut microbiota is essential to modulate immune response, influencing immunostimulatory or immunosuppressive reactions. So, the investigation of the microbiota-immunity axis in healthy and tumor mucosa is crucial to well understand the cancer development with positive relapses in prevention and treatment.
Project description:The RNA from two paired normal and colorectal tumor tissue were sequenced by Illumina genome analyzer. 0.8 to 1.1 million reads were generated. Sequencing data was aligned with human RNA, human mitochondrial DNA and human genomic DNA by BWA. Base calling and Phred-like score was calculated by SAMTools. Whole transcriptome sequence of paired normal and tumor tissues obtained from two colorectal cancer patients
Project description:Alterations in gut microbiota have been implicated in the pathogenesis of Colorectal Cancer (CRC). Here we collected fecal samples from 14 CRC patients and 14 healthy volunteer cohorts, and characterized their microbiota using label-free quantitative metaproteomics method. We have quantified 30,062 gut microbial protein groups, 91，902 peptides, and 195 genera of microbes, among which 341 proteins were found significantly different in abundance between the CRC patients and healthy volunteers. Our study demonstrates that gut bacteria involve in CRC pathogenesis not only via taxonomy abundance variations but also functional activity changes.
