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MedComm

IF: 10.69
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Nicotinamide mononucleotide protects STAT1 from oxidative stress‐induced degradation to prevent colorectal tumorigenesis

Published:21 November 2024 DOI: 10.1002/mco2.70006 PMID: 39575303
Ting Li, Chengting Luo, Zongyuan Liu, Jinyu Li, Meng Han, Ran Zhang, Yuling Chen, Haiteng Deng

Abstract

Colitis, accompanied by the accumulation of reactive oxygen species (ROS) in the intestinal tract, is a risk factor for colorectal cancer (CRC). Our previous studies indicate that nicotinamide mononucleotide (NMN) replenishment reduces chronic inflammation. In this study, we confirm that NMN supplementation reduces inflammatory cytokine levels and oxidative tissue damage in an azoxymethane/dextran sulfate sodium (AOM/DSS)-induced colitis-associated cancer (CAC) model. Mice treated with NMN developed fewer colon tumors than untreated animals under the same AOM/DSS treatment conditions. Quantitative proteomic analysis revealed a decrease in signal transducer and activator of transcription 1 (STAT1) expression in the CAC model. We demonstrate that STAT1 overexpression induces G1 arrest by downregulating CDK6 expression and suppressing tumor cell proliferation and migration. Of note, H2O2 induced trioxidation of the STAT1 protein and promoted its degradation, which was partially reversed by NMN supplementation. Upon H2O2 treatment, Cys155 in STAT1 was oxidized to sulfonic acid, whereas the mutation of Cys155 to alanine abolished ROS-mediated STAT1 degradation. These results indicate that oxidative stress induces STAT1 degradation in tumor cells and possibly in CAC tissues, whereas supplementation with NMN protects STAT1 from oxidation-induced degradation and prevents tumorigenesis. This study provides experimental evidence for the development of NMN-mediated chemoprevention strategies for CRC.

Substances (5)

Materials
Procduct Name CAS Molecular Formula Supplier Price
Urea 57-13-6 CH4N2O 777 suppliers $5.00-$9263.00
DL-Dithiothreitol 3483-12-3 C4H10O2S2 651 suppliers $7.00-$10710.00
Trypsin 9002-07-7 C35H47N7O10 453 suppliers $17.70-$24930.00
2-Iodoacetamide 144-48-9 C2H4INO 380 suppliers $10.00-$3550.00
FETUIN 9014-81-7 NULL 66 suppliers $37.07-$4380.00

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