Flap endonuclease-1 promotes pancreatic cancer progression via 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 in vitro, 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 in vitro, as well as xenograft tumor growth in vivo. Mechanistically, FEN1 regulated epithelial-mesenchymal transition through the AKT/mTOR signaling pathway.

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