Cancer Res Treat.
2025 Oct;57(4):1115-1134. 10.4143/crt.2024.959.
The Roles of Ninjurin1 and Estrogen in Modulating Azoxymethane/Dextran Sodium Sulfate–Induced Colitis-Associated Colorectal Cancer in Male Mice
- Affiliations
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- 1Department of Internal Medicine and Research Center for Sex- and Gender-Specific Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
- 2Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
- 3Department of Pathology, Hallym University Dongtan Sacred Heart Hospital, Hwaseong, Korea
- 4College of Pharmacy, Seoul National University, Seoul, Korea
- 5College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Korea
- 6Department of Vaccine Biotechnology, Andong National University, Andong, Korea
- 7Heart-Immune-Brain Network Research Center, Department of Life Sciences, Ewha Womans University, Seoul, Korea
- KMID: 2573002
- DOI: http://doi.org/10.4143/crt.2024.959
Abstract
- 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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