Nuclear Factor Erythroid 2-related Factor 2 Knockout Suppresses the Development of Aggressive Colorectal Cancer Formation Induced by Azoxymethane/Dextran Sulfate Sodium-Treatment in Female Mice

Abstract

Colorectal cancer (CRC) is the third leading cause of cancer-associated death in both male and female in the United States, with an estimation of 149,500 new cancer cases and 52,980 cancer deaths, in 2021 [1]. In South Korea, male have a higher incidence rate of age-adjusted CRC than female [2]. However, elderly female over 65 years of age show a higher mortality of CRC and a lower 5-year survival rate compared to their age-adjusted male [2]. CRC shows sex differences worldwide in the incidence and the developing site (proximal or distal colon), and underlying mechanisms [3].Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that plays a pivotal role in adaptive cellular defense response to a variety of stimuli such as oxidation, proteotoxic stress, metabolic stress, and inflammation [4,5]. In normal cells under non-stress conditions, Nrf2 levels and activity are kept relatively low by its rapid proteasomal degradation which is facilitated by Kelch-like ECH-associated protein 1 (Keap1) [6]. Under stress conditions, however, Nrf2

Changes in Microbial Community Composition Related to Sex and Colon Cancer by Nrf2 Knockout

“…The DAI was scored by two researchers in a blinded manner. These data have been reported by (Song et al, 2020a;Song et al, 2021).…”

“…The classification of adenoma and adenocarcinoma, and the specification of the depth of adenocarcinoma invasion into the colonic tissues as mucosal or submucosal invasion was performed by in a blinded manner. These data have been reported by (Song et al, 2020a;Song et al, 2021). In this study, tumor grade was scored as follows: 0, no tumor; 1, low-grade adenoma; 2, high-grade adenoma; 3, mucosal invasive adenocarcinoma; 4, submucosal invasive adenocarcinoma (Supplementary Dataset S2).…”

“…In the AOM/DSS-treated WT and Nrf2 KO groups, only mice with tumors were selected for microbial analysis. To understand the properties of the microbiota found in this study, we analyzed the correlation by taking previously reported results (DAI score, ELISA levels of MPO and IL-1β, and tumor number) from the same set of experiments ( Song et al., 2020a ; Song et al., 2021 ). Therefore, some of the data used in this study overlaps with the previous results.…”

“…Nrf2 heterozygous (Nrf2 +/− ) mice with a C57BL/6/129SV background ( Chan et al., 1996 ) were a kind gift from Prof. Y-J Surh (Seoul National University, Korea). WT (Nrf2 +/+ ) and homozygous Nrf2 KO (Nrf2 −/− ) mice were obtained by crossing Nrf2 heterozygous (Nrf2 +/− ) mice as previously described ( Song et al., 2020a ; Song et al., 2021 ). The Nrf2 KO mice used in the experiment were generated by Chan et al.…”

“…The animals were euthanized by CO 2 asphyxiation ( Figure 1A ). The previously reported analysis results of stool samples, which were obtained from the same experimental set, were used to analyze the gut microbiota composition in this study ( Song et al., 2020a ; Song et al., 2021 ).…”