Basic Study
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Jul 15, 2025; 17(7): 104402
Published online Jul 15, 2025. doi: 10.4251/wjgo.v17.i7.104402
Flap endonuclease-1 promotes pancreatic cancer progression via AKT/mTOR signaling pathway
Yu Xia, Na Guo, Cheng-Lou Zhu, Jie-Yun Gao, Ming-Xu Da
Yu Xia, Na Guo, Cheng-Lou Zhu, Ming-Xu Da, The First School of Clinical Medicine, Lanzhou University, Lanzhou 730000, Gansu Province, China
Jie-Yun Gao, Department of Clinical Teaching, Gansu Provincial Hospital, Lanzhou 730000, Gansu Province, China
Ming-Xu Da, Department of Surgical Oncology, Gansu Provincial Hospital, Lanzhou 730000, Gansu Province, China
Co-first authors: Yu Xia and Na Guo.
Co-corresponding authors: Jie-Yun Gao and Ming-Xu Da.
Author contributions: Xia Y and Guo N conceived and supervised the study; Xia Y performed the experiments and drafted the manuscript; Zhu CL and Guo N were responsible for animal care, procedures, and sample collection; Guo N and Xia Y carried out the experimental work; Da MX and Zhu CL contributed to data cleaning and analysis; Da MX and Gao JY revised and polished the manuscript, and Gao JY also provided financial support for the project. All authors reviewed and approved the final version of the manuscript. Xia Y and Guo N contributed equally to this work as co-first authors. Da MX and Gao JY are designated as co-corresponding authors, with Da MX serving as the primary contact. Dr. Da MX led the data analysis, manuscript revision, and provided intellectual oversight throughout the research process. Dr. Gao JY played a vital supporting role by providing full financial coverage for publication fees and partially funding the experimental work. Moreover, she contributed to research coordination and offered critical feedback during key decision points in the study. Given these distinct and complementary roles, it is justified to designate both as co-corresponding authors, with Da MX serving as the primary contact.
Supported by Youth Science and Technology Fund Program of the Natural Science Foundation of Gansu Province, No. 21JR7RA645 and No. 23JRRA1317.
Institutional review board statement: The study was approved by the Ethics Committee of Gansu Provincial Hospital (approval number: 2024-418), with informed consent obtained from all participants.
Institutional animal care and use committee statement: This animal study was approved by the Laboratory Animal Ethics Committee of Lanzhou Veterinary Research Institute (LVRIAEC-2024-042).
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
ARRIVE guidelines statement: The authors have read the ARRIVE Guidelines, and the manuscript was prepared and revised according to the ARRIVE Guidelines.
Data sharing statement: The datasets generated and/or analyzed during the current study are not publicly available but are available from the corresponding author upon reasonable request.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Ming-Xu Da, The First School of Clinical Medicine, Lanzhou University, No. 222 Tianshui South, Chengguan District, Lanzhou 730000, Gansu Province, China. ldyy_damx@lzu.edu.cn
Received: December 20, 2024
Revised: April 8, 2025
Accepted: May 29, 2025
Published online: July 15, 2025
Processing time: 207 Days and 7.7 Hours
Abstract
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.

Keywords: Flap endonuclease-1; Pancreatic cancer; AKT/mTOR signaling pathway; Proliferation; Migration; Invasion

Core Tip: This study elucidates the oncogenic role of flap endonuclease-1 (FEN1) in pancreatic cancer (PC), demonstrating its ability to promote cancer cell proliferation, migration, and invasion through modulation of the AKT/mTOR signaling pathway. Elevated FEN1 expression is closely associated with poor prognosis in PC patients, and FEN1 significantly enhances tumor growth both in vitro and in vivo. RNA sequencing, transcriptome analysis, and functional experiments further validate that the oncogenic effects of FEN1 are partially mediated by the activation of the AKT/mTOR signaling pathway, providing compelling evidence for FEN1 as a potential therapeutic target in PC.