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

IF 2.5 4区 医学 Q2 GASTROENTEROLOGY & HEPATOLOGY
Yu Xia, Na Guo, Cheng-Lou Zhu, Jie-Yun Gao, Ming-Xu Da
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引用次数: 0

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.

皮瓣内切酶-1通过AKT/mTOR信号通路促进胰腺癌进展。
背景:胰腺癌(PC)是最致命的恶性肿瘤之一。虽然皮瓣内切酶-1 (FEN1)与多种癌症有关,但其在PC中的作用尚不清楚。目的:探讨FEN1在前列腺癌进展中的生物学功能及机制。方法:应用Gene expression Omnibus、The Cancer Genome Atlas和Genotype-Tissue expression数据库分析FEN1的表达及其预后意义。用慢病毒载体敲低或过表达FEN1。在体外评估细胞增殖、迁移和侵袭,在裸鼠异种移植物中评估致瘤性。通过rna测序和western blot分析验证分子机制。结果:FEN1在PC组织中表达明显上调,与预后不良相关。FEN1在体外促进PC细胞增殖、迁移和侵袭,在体内促进异种移植物肿瘤生长。机制上,FEN1通过AKT/mTOR信号通路调节上皮-间质转化。结论:FEN1通过AKT/mTOR信号通路在PC进展中起致癌驱动作用,提示其作为治疗靶点的潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
World Journal of Gastrointestinal Oncology
World Journal of Gastrointestinal Oncology Medicine-Gastroenterology
CiteScore
4.20
自引率
3.30%
发文量
1082
期刊介绍: The World Journal of Gastrointestinal Oncology (WJGO) is a leading academic journal devoted to reporting the latest, cutting-edge research progress and findings of basic research and clinical practice in the field of gastrointestinal oncology.
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