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Original Articles
- Gastrointestinal cancer
- The Roles of Ninjurin1 and Estrogen in Modulating Azoxymethane/Dextran Sodium Sulfate–Induced Colitis-Associated Colorectal Cancer in Male Mice
- Chin-Hee Song, Nayoung Kim, Ryoung Hee Nam, Jae Young Jang, Eun Hye Kim, Sungchan Ha, Eun Shin, Ha-Na Lee, Hoon Choi, Kyu-Won Kim, Sejin Jeon, Goo Taeg Oh
- Cancer Res Treat. 2025;57(4):1115-1134. Published online January 13, 2025
- DOI: https://doi.org/10.4143/crt.2024.959
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Abstract
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ePub - Purpose
Nerve injury–induced protein 1 (Ninj1) is associated with inflammation and tumor progression and shows increased expression in various cancers. This study aimed to investigate the role of Ninj1 in colitis-associated colorectal cancer (CRC) by focusing on its interaction with 17β-estradiol (E2).
Materials and Methods
Using an azoxymethane (AOM)/dextran sodium sulfate (DSS) mouse model of colitis-associated CRC, wild-type (WT) and Ninj1 knockout (KO) male mice were treated with or without E2.
Results
At week 2, Ninj1 KO mice exhibited attenuated colitis symptoms than WT mice following AOM/DSS treatment. E2 administration significantly alleviated these symptoms in both WT and Ninj1 KO mice, with reductions in the disease activity index, colon length shortening, and histopathological damage. The levels of pro-inflammatory mediators were reduced by E2 treatment in both groups, with the Ninj1 KO group showing a more pronounced response. At week 13, tumor development in Ninj1 KO mice was significantly lower than that in WT mice, particularly in the distal colon. E2 treatment inhibited tumor formation in WT mice and had a stronger inhibitory effect on distal colon tumorigenesis in Ninj1 KO mice. Immune cell populations, including the populations of macrophages and T cells, were also modulated by E2 in WT mice; however, these effects were diminished in Ninj1 KO mice.
Conclusion
These findings suggest that Ninj1 plays a role in modulating colitis and CRC progression, with E2 exerting anti-inflammatory and anti-tumorigenic effects that are influenced by Ninj1 status.
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- Changes in Gut Microbiome upon Orchiectomy and Testosterone Administration in AOM/DSS-Induced Colon Cancer Mouse Model
- Chin-Hee Song, Nayoung Kim, Ryoung Hee Nam, Soo In Choi, Jae Young Jang, Ha-Na Lee
- Cancer Res Treat. 2023;55(1):196-218. Published online July 1, 2022
- DOI: https://doi.org/10.4143/crt.2022.080
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Abstract
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Supplementary MaterialPubReaderePub - Purpose
Sex hormones are known to affect the gut microbiota. Previously, we reported that endogenous and exogenous testosterone are associated with colorectal cancer (CRC) development and submucosal invasion. In the present study, we investigated whether the gut microbiota is affected by orchiectomy (ORX) and testosterone propionate (TP) administration using an azoxymethane/dextran sulfate sodium (AOM/DSS)-induced CRC mouse model.
Materials and Methods
Gut microbiota was evaluated by means of 16S rRNA gene sequencing of stool DNA extracted from feces that were obtained at 13 weeks after AOM injection (from 22-week-old animals) and stored in a gas-generating pouch.
Results
The increase in microbial diversity (Chao1 and Phylogenetic Diversity index) and Firmicutes/Bacteroidetes (F/B) ratio upon AOM/DSS treatment in ORX mice was significantly decreased by TP supplementation. The ratio of commensal bacteria to opportunistic pathogens was lower in the TP-administered females and ORX mice than in the AOM/DSS group. Opportunistic pathogens (Mucispirillum schaedleri or Akkermansia muciniphila) were identified only in the TP group. In addition, microbial diversity and F/B ratio were higher in male controls than in female and ORX controls. Flintibacter butyricus, Ruminococcus bromii, and Romboutsia timonensis showed similar changes in the male control group as those in the female and ORX controls.
Conclusion
In conclusion, testosterone determines the dysbiosis of gut microbiota, which suggests that it plays a role in the sex-related differences in colorectal carcinogenesis. -
Citations
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Aris Kaltsas, Ilias Giannakodimos, Eleftheria Markou, Konstantinos Adamos, Marios Stavropoulos, Zisis Kratiras, Athanasios Zachariou, Fotios Dimitriadis, Nikolaos Sofikitis, Michael Chrisofos
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Cell & Bioscience.2025;[Epub] CrossRef - Sex differences in colorectal cancer: with a focus on sex hormone–gut microbiome axis
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Cell Communication and Signaling.2024;[Epub] CrossRef - Comparison of the fecal bacterial microbiota in mice, rats, and pigs after oral administration of alpha-glycosyl isoquercitrin
Hong Liu, Ryo Inoue, Mihoko Koyanagi, Shim-mo Hayashi, Gen Watanabe, Kentaro Nagaoka
The Journal of Toxicological Sciences.2024; 49(4): 151. CrossRef - Gut Microbes in Polycystic Ovary Syndrome and Associated Comorbidities; Type 2 Diabetes, Non-Alcoholic Fatty Liver Disease (NAFLD), Cardiovascular Disease (CVD), and the Potential of Microbial Therapeutics
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Probiotics and Antimicrobial Proteins.2024; 16(5): 1744. CrossRef - Role of sex steroids in colorectal cancer: pathomechanisms and medical applications
Jianglan Wu
American Journal of Cancer Research.2024; 14(7): 3200. CrossRef - Gender-affirming hormonal therapy induces a gender-concordant fecal metagenome transition in transgender individuals
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Anna Drzazga, Przemysław Bernat, Adriana Nowak, Marcin Szustak, Eliza Korkus, Edyta Gendaszewska-Darmach, Maria Koziołkiewicz
Biomedicine & Pharmacotherapy.2024; 180: 117467. CrossRef - Role of intestinal testosterone-degrading bacteria and 3/17β-HSD in the pathogenesis of testosterone deficiency-induced hyperlipidemia in males
Jun Tao, Wen Dai, Yongnan Lyu, Hang Liu, Juan Le, Ting Sun, Qian Yao, Zhiming Zhao, Xuejun Jiang, Yan Li
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Chinese Science Bulletin.2024; 69(35): 5142. CrossRef - Direct and indirect effects of estrogens, androgens and intestinal microbiota on colorectal cancer
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Frontiers in Cellular and Infection Microbiology.2024;[Epub] CrossRef - From-Toilet-to-Freezer: A Review on Requirements for an Automatic Protocol to Collect and Store Human Fecal Samples for Research Purposes
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Biomedicines.2023; 11(10): 2658. CrossRef - Murine models of colorectal cancer: the azoxymethane (AOM)/dextran sulfate sodium (DSS) model of colitis-associated cancer
Dzhuliia Dzhalilova, Natalia Zolotova, Nikolai Fokichev, Olga Makarova
PeerJ.2023; 11: e16159. CrossRef
- The Role of Gut Microbiota Dysbiosis in Erectile Dysfunction: From Pathophysiology to Treatment Strategies
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- 253 Download
- 19 Web of Science
- 17 Crossref
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