ZFP90 drives the initiation of colitis-associated colorectal cancer via a microbiota-dependent strategy.

Gut Microbes

State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Published: January 2022

Chronic inflammation and gut microbiota dysbiosis are risk factors for colorectal cancer. In clinical practice, patients with inflammatory bowel disease (IBD) have a greatly increased risk of developing colitis-associated colorectal cancer (CAC). However, the underlying mechanism of the initiation of CAC remains unknown. Systematic analyses using an existing genome-wide association study (GWAS) and conditional deletion of (encoding zinc finger protein 90 homolog) in a CAC mouse model indicated that is a putative oncogene in CAC development.Strikingly, depletion of the gut microbiota eliminated the tumorigenic effect of in the CAC mouse model. Moreover, fecal microbiota transplantation demonstrated that promoted CAC dependent on the gut microbiota. Analysis of 16s rDNA sequences in fecal specimens from the CAC mouse model allowed us to speculate that a -defined microbiota might mediate the oncogenic role of in the development of CAC. Mechanistic studies revealed accelerated CAC development through the TLR4-PI3K-AKT-NF-κB pathway. Our findings revealed the crucial role of the -microbiota-NF-κB axis in creating a tumor-promoting environment and suggested therapeutic targets for CAC prevention and treatment.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8115455PMC
http://dx.doi.org/10.1080/19490976.2021.1917269DOI Listing

Publication Analysis

Top Keywords

colorectal cancer
12
gut microbiota
12
cac mouse
12
mouse model
12
cac
10
colitis-associated colorectal
8
microbiota
5
zfp90 drives
4
drives initiation
4
initiation colitis-associated
4

Similar Publications

E. Coli cytotoxic necrotizing factor-1 promotes colorectal carcinogenesis by causing oxidative stress, DNA damage and intestinal permeability alteration.

J Exp Clin Cancer Res

January 2025

Department of Cardiovascular, Endocrine-Metabolic Diseases and Aging, Istituto Superiore di Sanità, Rome, Italy.

Background: Bacterial toxins are emerging as promising hallmarks of colorectal cancer (CRC) pathogenesis. In particular, Cytotoxic Necrotizing Factor 1 (CNF1) from E. coli deserves special consideration due to the significantly higher prevalence of this toxin gene in CRC patients with respect to healthy subjects, and to the numerous tumor-promoting effects that have been ascribed to the toxin in vitro.

View Article and Find Full Text PDF

Efficacy and safety of neoadjuvant bevacizumab plus chemotherapy in locally advanced gastric cancer patients: a retrospective, comparative study.

World J Surg Oncol

January 2025

Colorectal Surgery Department, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University/ Hunan Cancer Hospital, No. 283 Tongzipo Road, Yuelu District, Changsha, Hunan, 410013, China.

Objective: The clinical benefits of neoadjuvant bevacizumab plus chemotherapy in locally advanced gastric cancer patients are controversial. This study intended to evaluate the efficacy and safety of neoadjuvant bevacizumab plus chemotherapy in these patients.

Methods: In this retrospective study, 71 locally advanced gastric cancer patients receiving neoadjuvant bevacizumab plus chemotherapy or neoadjuvant chemotherapy alone were divided into bevacizumab plus chemo group (N = 23) and chemo group (N = 48).

View Article and Find Full Text PDF

Background: Tumor microenvironment (TME), particularly immune cell infiltration, programmed cell death (PCD) and stress, has increasingly become a focal point in colorectal cancer (CRC) treatment. Uncovering the intricate crosstalk between these factors can enhance our understanding of CRC, guide therapeutic strategies, and improve patient prognosis.

Methods: We constructed an immune-related cell death and stress (ICDS) prognostic model utilizing machine learning methodologies.

View Article and Find Full Text PDF

Background: DNA hypomethylation and uracil misincorporation into DNA, both of which have a very important correlation with colorectal carcinogenesis. Folate plays a crucial role in DNA synthesis, acting as a coenzyme in one-carbon metabolism, which involves the synthesis of purines, pyrimidines, and methyl groups. MTHFR, a key enzyme in folate metabolism, has been widely studied in relation to neural tube defects and hypertension, but its role in colorectal cancer remains underexplored.

View Article and Find Full Text PDF

Background: Early detection and diagnosis of cancer are vital to improving outcomes for patients. Artificial intelligence (AI) models have shown promise in the early detection and diagnosis of cancer, but there is limited evidence on methods that fully exploit the longitudinal data stored within electronic health records (EHRs). This review aims to summarise methods currently utilised for prediction of cancer from longitudinal data and provides recommendations on how such models should be developed.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!