Identification of novel Nrf2 target genes as prognostic biomarkers in colitis-associated colorectal cancer in Nrf2-deficient mice

Publication date: Available online 16 October 2019Source: Life SciencesAuthor(s): Ahmed Hammad, Zhao-Hong Zheng, Yang Gao, Akhileshwar Namani, Hong-Fei Shi, Xiuwen TangAbstractAimsColorectal cancer (CRC) is the third most common cancer worldwide. Nuclear factor erythroid 2-related factor 2 (Nrf2), a master regulator of many cytoprotective genes, plays a protective role in carcinogenesis. Recent studies have identified a specific gene-expression signature regulated by the Nrf2 pathway in lung adenocarcinoma and head-and-neck squamous cell cancer. However, the roles of Nrf2 in the development of colitis-associated colorectal cancer (CACC) have not been well characterized. Nrf2 target genes as prognostic biomarkers in CACC remain to be explored. Thus, this work aimed to identify the molecular changes that occur during mouse CACC progression to facilitate the development of diagnostic and prognostic biomarkers.Main methodsThe CACC model was established using azoxymethane (AOM) with dextran sulfate sodium salt (DSS) in BALB/c mice for 3 weeks to induce colitis-associated adenoma (CAA, early stage) and for 9 weeks to induce colitis-associated carcinoma (CAC, late stage). Using RNA-sequencing and bioinformatics analyses we examined the mRNA expression profiles of 6 groups: wild-type control (WT-C), WT-CAA, WT-CAC, Nrf2 knockout control (Nrf2KO–C), Nrf2KO-CAA, and Nrf2KO-CAC.Key findingsIn the AOM/DSS model of colitis-associated tumorigenesis, Nrf2−/− mice showed a phenotype si...
Source: Life Sciences - Category: Biology Source Type: research