FEN1 通过调控 Wnt/β-catenin 信号通路促进胆管癌的进展。

FEN1 promotes cancer progression of cholangiocarcinoma by regulating the Wnt/β-catenin signaling pathway.

机构信息

Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao, Shandong 266000, China.

Department of Endocrinology and Metabolism, The Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao, Shandong 266000, China.

出版信息

Dig Liver Dis. 2024 Apr;56(4):695-704. doi: 10.1016/j.dld.2023.08.050. Epub 2023 Aug 28.

DOI:10.1016/j.dld.2023.08.050

PMID:37648642

Abstract

PURPOSE

Cholangiocarcinoma (CHOL) comprises a cluster of highly heterogeneous malignant biliary tumors. Flap endonuclease-1 (FEN1) is a member of the Rad2 structure-specific nuclease family. This study aimed to explore the biological functions and mechanisms of FEN1 in CHOL.

METHODS

FEN1 expression was analyzed in tissues of patients with CHOL and FEN1 mutations. We observe the influence of FEN1 on cellular proliferation, migration, and invasion, as well as on DNA damage repair and glycolysis. Western blotting was performed to determine the regulatory mechanism of FEN1 in CHOL progression.

RESULTS

FEN1 was highly expressed in the cancer tissues of CHOL patients. The high mutation rate of FEN1 in CHOL tissues was mainly due to the amplified repeats. FEN1 promotes the proliferation, migration, and invasion of HUCCT1 and QBC939 cells. In addition, FEN1 induced DNA damage repair and aerobic glycolysis in CHOL cells. FEN1 also promoted xenograft tumor growth in vivo. Moreover, we showed that FEN1 mediated the epithelial-mesenchymal transition (EMT) of CHOL. FEN1-mediated EMT was found to be transduced by the Wnt/β-catenin signaling pathway.

CONCLUSION

FEN1 was significantly overexpressed in CHOL tissues, and FEN1 regulates the progression of CHOL through the Wnt/β-catenin signaling pathway.

摘要

目的

胆管癌（CHOL）由一群高度异质的恶性胆道肿瘤组成。核酸内切酶 1（FEN1）是 Rad2 结构特异性核酸酶家族的成员。本研究旨在探讨 FEN1 在 CHOL 中的生物学功能和机制。

方法

分析 CHOL 患者组织和 FEN1 突变组织中 FEN1 的表达。观察 FEN1 对细胞增殖、迁移和侵袭以及 DNA 损伤修复和糖酵解的影响。Western blot 用于确定 FEN1 在 CHOL 进展中的调节机制。

结果

FEN1 在 CHOL 患者的癌组织中高表达。FEN1 在 CHOL 组织中的高突变率主要归因于扩增的重复序列。FEN1 促进 HUCCT1 和 QBC939 细胞的增殖、迁移和侵袭。此外，FEN1 诱导 CHOL 细胞中的 DNA 损伤修复和有氧糖酵解。FEN1 还促进了体内异种移植肿瘤的生长。此外，我们表明 FEN1 介导了 CHOL 的上皮-间充质转化（EMT）。发现 FEN1 介导的 EMT 是通过 Wnt/β-catenin 信号通路转导的。