Background: MYT1 (Myelin Transcription Factor 1) is a transcription factor that plays a pivotal role in regulating the G2/M cell cycle checkpoint, a critical phase in cell division where cells prepare to enter mitosis. Proper regulation of this checkpoint is essential for maintaining genomic stability and preventing uncontrolled cell proliferation. In various cancers, including breast cancer, MYT1 is often overexpressed, which has been associated with enhanced DNA repair mechanisms and increased cell survival. This overexpression contributes to therapy resistance, making tumors less responsive to conventional treatments such as chemotherapy and radiation. Consequently, high levels of MYT1 expression are linked to poor clinical outcomes, including increased metastasis and reduced patient survival rates. Urolithin B (UB) is a metabolite produced by gut bacteria from ellagitannins, compounds found in foods such as pomegranates and walnuts. Objective: MYT1 is a crucial regulator of the G2/M cell cycle checkpoint. Its overexpression in various cancers promotes therapy resistance by enhancing DNA repair and cell survival, leading to poor clinical outcomes and increased metastasis. Urolithin B (UB), a metabolite derived from gut bacteria processing ellagitannins found in foods like pomegranates and walnuts, has shown promise in combating cancer by reducing inflammation and oxidative stress. This study aimed to investigate the potential of UB to target MYT1 in invasive breast carcinoma, exploring its therapeutic implications in this context. Methods: The expression of MYT1 was examined by a web portal in tissues from breast invasive carcinoma versus normal samples. Upon retrieving the structure of MYT1 from PDB and UB from PubChem, molecular docking was performed to evaluate the binding affinity of UB with the active site of MYT1. Results: Analysis of MYT1 expression indicated that this target was considerably upregulated in breast invasive carcinoma samples (n=1097) compared to normal specimens (n=114), with a p-value of 1.62E-12. Additionally, results of molecular docking revealed a JAMDA score of -2.15 for UB interacting with residues in the cofactor binding site of MYT1, including Thr187, Glu188, Phe240, Leu116, and Val124. Conclusion: MYT1 is a potential therapeutic target to combat invasive breast carcinoma. the high-affinity binding interaction between UB and MYT1 highlights this microbiome-derived metabolite as a promising candidate for developing novel therapeutic strategies.

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