Abstract 3107: Nuciferine inhibits proliferation, invasion, and migration of colorectal cancer cells via the RBM15-JAG2 axis

Background: Colon cancer is the third most common cancer globally, with high incidence and mortality rates. Dietary supplementation therapy, due to its safety, painlessness, high patient acceptance, and practical efficiency, often becomes an adjunctive treatment for colon cancer. Therefore, developing new health foods and exploring new treatment mechanisms are of great significance for the adjuvant treatment of colon cancer. Methods: This study investigated the effects of nuciferine treatment and RBM15 inhibition on the m6A modification of JAG2 using MeRIP-qPCR and actinomycin D experiments. Additionally, the impact on the biological behavior of colorectal cancer cells was assessed through plate colony formation assays, scratch assays, Transwell assays, and Western blot analyses. Results: In this study, through transcriptome sequencing, RBM15 was discovered as a potential target of Nuciferine. The RBM15/JAG2 regulatory axis was found through bioinformatics analysis. Through total m6A detection, MeRip-qPCR, and actinomycin D experiments, it was confirmed that Nuciferine inhibits colon cancer by suppressing the m6A modification of JAG2 by methyltransferase RBM15. Additionally, plate colony experiments, scratch experiments, Transwell experiments, and Western blot experiments demonstrated that Nuciferine can inhibit the proliferation, invasion, and metastasis of colon cancer. In vivo experiments showed that Nuciferine has the effect of inhibiting the proliferation and metastasis of colon cancer. Conclusion: The results of this study indicate that nuciferine inhibits the proliferation, invasion, and migration of colorectal cancer cells by regulating RBM15 expression to mediate JAG2 m6A methylation. Therefore, Nuciferine is an ideal health food for adjuvant treatment of colon cancer. Citation Format: KaiHe Zhu, JiaPeng RU, Yichen Zhang, Fangyue Guo, Mengying Liu, Shize Xiao, Xufeng Wang, Jing Wu, Peizhi Ma, Pei Li, Shanfeng Zhang. Nuciferine inhibits proliferation, invasion, and migration of colorectal cancer cells via the RBM15-JAG2 axis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3107.