USP8 promotes the tumorigenesis of intrahepatic cholangiocarcinoma via stabilizing OGT.

IF 5.3 2区医学 Q1 ONCOLOGY

Cancer Cell International Pub Date : 2024-07-07 DOI:10.1186/s12935-024-03370-w

Guo Long, Dong Wang, Jianing Tang, Kuan Hu, Ledu Zhou

引用次数: 0

Abstract

Ubiquitination was considered to be a crucial factor in intrahepatic cholangiocarcinoma (iCCA) development. Herein, we identified Ubiquitin-specific peptidase 8 (USP8) as a key regulator for promoting the tumorigenesis of iCCA cell via stabilizing OGT. USP8 was overexpressed in human tumor tissues and correlated with worse survival. Moreover, the mass spectrometry and co-immunoprecipitation analysis indicated that USP8 interacted with OGT. USP8 worked as a bona fide deubiquitylase of OGT. It stabilized OGT in a deubiquitylation activity-dependent manner. Meanwhile, DUB-IN3, the USP8 inhibitor, could also restrain the malignancy of intrahepatic cholangiocarcinoma. In addition, USP8 depletion promoted the response of iCCA to pemigatinib. In conclusion, our findings pointed to a previously undocumented catalytic role for USP8 as a deubiquitinating enzyme of OGT. The USP8-OGT axis could be a potential target for iCCA therapy.

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USP8 通过稳定 OGT 促进肝内胆管癌的肿瘤发生。

泛素化被认为是肝内胆管癌（iCCA）发生的关键因素。在此，我们发现泛素特异性肽酶 8（USP8）是通过稳定 OGT 促进 iCCA 细胞肿瘤发生的关键调控因子。USP8 在人类肿瘤组织中过表达，并与生存率下降相关。此外，质谱分析和共沉淀分析表明，USP8 与 OGT 相互作用。USP8 是 OGT 的真正去泛素化酶。它以依赖于去泛素化活性的方式稳定 OGT。同时，USP8抑制剂DUB-IN3也能抑制肝内胆管癌的恶性发展。此外，USP8耗竭可促进iCCA对pemigatinib的反应。总之，我们的研究结果表明，USP8作为OGT的去泛素化酶，具有以前未曾记载的催化作用。USP8-OGT 轴可能是治疗 iCCA 的潜在靶点。

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

Cancer Cell International ONCOLOGY-

CiteScore

10.90

自引率

1.70%

发文量

360

审稿时长

1 months

期刊介绍： Cancer Cell International publishes articles on all aspects of cancer cell biology, originating largely from, but not limited to, work using cell culture techniques. The journal focuses on novel cancer studies reporting data from biological experiments performed on cells grown in vitro, in two- or three-dimensional systems, and/or in vivo (animal experiments). These types of experiments have provided crucial data in many fields, from cell proliferation and transformation, to epithelial-mesenchymal interaction, to apoptosis, and host immune response to tumors. Cancer Cell International also considers articles that focus on novel technologies or novel pathways in molecular analysis and on epidemiological studies that may affect patient care, as well as articles reporting translational cancer research studies where in vitro discoveries are bridged to the clinic. As such, the journal is interested in laboratory and animal studies reporting on novel biomarkers of tumor progression and response to therapy and on their applicability to human cancers.