Flap endonuclease-1 promotes pancreatic cancer progression AKT/mTOR signaling pathway.

BACKGROUND

Pancreatic cancer (PC) remains one of the most lethal malignancies. While flap endonuclease-1 (FEN1) has been implicated in various cancers, its role in PC remains unclear.

AIM

To investigate the biological functions and mechanisms of FEN1 in PC progression.

METHODS

FEN1 expression and its prognostic significance were analyzed using Gene Expression Omnibus, The Cancer Genome Atlas, and Genotype-Tissue Expression databases. FEN1 was knocked down or overexpressed in PC cell lines using lentiviral vectors. Cell proliferation, migration, and invasion were assessed , while tumorigenicity was evaluated in nude mouse xenografts. Molecular mechanisms were explored through RNA-sequencing and validated by western blot analysis.

RESULTS

FEN1 was significantly upregulated in PC tissues and correlated with poor prognosis. FEN1 promoted PC cell proliferation, migration, and invasion , as well as xenograft tumor growth . Mechanistically, FEN1 regulated epithelial-mesenchymal transition through the AKT/mTOR signaling pathway.

CONCLUSION

FEN1 functions as an oncogenic driver in PC progression the AKT/mTOR signaling pathway, suggesting its potential as a therapeutic target.