Targeting FMO3 suppresses the malignant phenotype of colorectal cancer: evidence from bioinformatics to functional experiments

AIMS Flavin-containing monooxygenase 3 (FMO3) is a key metabolic enzyme involved in endogenous metabolism; however, its role in colorectal cancer (CRC) remains poorly understood. This study aimed to investigate the expression pattern, biological function, and potential clinical relevance of FMO3 in CRC.

MATERIALS AND METHODS Publicly available transcriptomic datasets were analyzed to assess FMO3 expression and its association with clinical characteristics. Immunohistochemistry and in vitro functional assays were performed to evaluate the effects of FMO3 on CRC cell proliferation, cell-cycle progression, migration, and invasion. Bioinformatics analyses were used to explore potential signaling pathways and immune-related associations.

RESULTS FMO3 was significantly upregulated in CRC tissues and cell lines and was associated with unfavorable clinicopathological features and poor prognosis. Silencing of FMO3 inhibited CRC cell proliferation by inducing G0/G1 cell-cycle arrest and suppressed migration and invasion by reversing epithelial-mesenchymal transition-related phenotypes. Mechanistically, FMO3 depletion attenuated PI3K/AKT signaling activity. In addition, FMO3 expression was correlated with immune cell infiltration patterns and immune checkpoint-related molecules.

CONCLUSIONS FMO3 promotes malignant progression of colorectal cancer and may serve as a potential biomarker and therapeutic target. Further in vivo and mechanistic studies are warranted to validate these findings.