Molecular biological role of epithelial splicing regulatory protein 1 in intrahepatic cholangiocarcinoma.

IF 3.9 3区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Hepatology Research Pub Date : 2024-07-22 DOI:10.1111/hepr.14096

Takahiro Haruna, Mitsuhiro Kudo, Kousuke Ishino, Junji Ueda, Yukako Shintani-Domoto, Daigo Yoshimori, Takenori Fuji, Yoko Kawamoto, Kiyoshi Teduka, Taeko Kitamura, Hiroshi Yoshida, Ryuji Ohashi

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引用次数: 0

Abstract

Aim: Epithelial splicing regulatory protein 1 (ESRP1) regulates tumor progression and metastasis through the epithelial‒mesenchymal transition by interacting with zinc finger E-box binding 1 (ZEB1) and CD44 in cancers. However, the role of ESRP1 in intrahepatic cholangiocarcinoma (iCCA) remains unclear.

Methods: Three iCCA cell lines (HuCCT-1, SSP-25, and KKU-100) were analyzed using small interfering RNA to investigate the molecular biological functions of ESRP1 and ZEB1. The association between clinicopathological features and the expression of ESRP1 and ZEB1 in iCCA tissues was analyzed immunohistochemically. Proteomic analysis was performed to identify molecules related to ESRP1 expression.

Results: ESRP1 expression was upregulated in HuCCT-1 and SSP-25 cells. Cell migration and invasion were enhanced, and the expression of ZEB1 and CD44s (CD44 standard) isoforms were upregulated in the ESRP1 silencing cells. Moreover, ESRP1 silencing increased the expression of N-cadherin and vimentin, indicating the presence of mesenchymal properties. Conversely, ZEB1 silencing increased the expression of ESRP1 and CD44v (CD44 variant) isoforms. Immunohistochemical analysis revealed that a lower ESRP1-to-ZEB1 expression ratio was associated with poor recurrence-free survival in patients with iCCA. Flotillin 2, a lipid raft marker related to epithelial‒mesenchymal transition, was identified as a protein related to the interactive feedback loop in proteomic analysis.

Conclusions: ESRP1 suppresses tumor progression in iCCA by interacting with ZEB1 and CD44 to regulate epithelial‒mesenchymal transition.

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上皮剪接调节蛋白 1 在肝内胆管癌中的分子生物学作用

目的：上皮剪接调控蛋白1（epithelial splicing regulatory protein 1，ERP1）通过与癌症中的锌指E盒结合1（zinc finger E-box binding 1，ZEB1）和CD44相互作用，通过上皮-间质转化调节肿瘤的进展和转移。然而，ESRP1在肝内胆管癌（iCCA）中的作用仍不清楚：方法：使用小干扰 RNA 分析了三种 iCCA 细胞系（HuCCT-1、SSP-25 和 KKU-100），以研究 ESRP1 和 ZEB1 的分子生物学功能。免疫组化分析了临床病理特征与 iCCA 组织中 ESRP1 和 ZEB1 表达的关系。通过蛋白质组学分析确定与ESRP1表达相关的分子：结果：ESRP1在HuCCT-1和SSP-25细胞中表达上调。结果：ESRP1在HuCCT-1和SSP-25细胞中表达上调，细胞迁移和侵袭增强，ZEB1和CD44s（CD44标准）同工酶表达上调。此外，沉默 ESRP1 还增加了 N-粘连蛋白和波形蛋白的表达，表明存在间充质特性。相反，ZEB1沉默会增加ESRP1和CD44v（CD44变体）同工酶的表达。免疫组化分析表明，ESRP1与ZEB1的表达比值越低，iCCA患者的无复发生存率越低。在蛋白质组分析中，与上皮-间质转化相关的脂筏标记物Flotillin 2被确定为与交互反馈环路相关的蛋白质：结论：ESRP1通过与ZEB1和CD44相互作用来调控上皮-间质转化，从而抑制iCCA的肿瘤进展。

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

Hepatology Research 医学-胃肠肝病学

CiteScore

8.30

自引率

14.30%

发文量

124

审稿时长

1 months

期刊介绍： Hepatology Research (formerly International Hepatology Communications) is the official journal of the Japan Society of Hepatology, and publishes original articles, reviews and short comunications dealing with hepatology. Reviews or mini-reviews are especially welcomed from those areas within hepatology undergoing rapid changes. Short communications should contain concise definitive information.