OTUD7B 促进细胞迁移和侵袭，可预测胃癌的不良预后。

IF 2.9 4区医学 Q2 PATHOLOGY

Pathology, research and practice Pub Date : 2024-10-31 DOI:10.1016/j.prp.2024.155689

Xiao-Li Liu , Shan-Yu Zhao , Ming-Hui Zhang , Ping-Zhao Zhang , Xiu-Ping Liu

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引用次数: 0

摘要

背景：OTUD7B是卵巢肿瘤（OTU）蛋白超家族的成员，作为一种去泛素化酶发挥作用，与包括肿瘤在内的多种生物过程和疾病相关。本研究旨在探讨 OTUD7B 在胃癌（GC）中的表达模式、预后意义、功能作用及其内在机制：采用生物信息学、临床病例回顾和分子实验相结合的方法，我们评估了 OTUD7B 在 GC 中 mRNA 和蛋白水平的表达。我们研究了 OTUD7B 表达与 GC 患者临床病理特征之间的关系。此外，我们还利用体外实验评估了 OTUD7B 对 GC 细胞迁移和侵袭能力的影响。研究人员还进行了 RNA 测序分析，以确定 GC 中与 OTUD7B 相关的关键基因和通路：结果：研究发现，OTUD7B在GC中的mRNA和蛋白质水平均显著过表达。较高水平的OTUD7B与肿瘤TNM分期晚期、组织学分级较高以及淋巴/静脉侵犯呈正相关。这些相关性表明 GC 患者的总生存期（OS）和无病生存期（DFS）较差。体外实验显示，基因敲除 OTUD7B 会显著降低 GC 细胞的迁移和侵袭，而过表达 OTUD7B 则会增强细胞的迁移和侵袭。此外，RNA 测序和生物信息学分析表明，缺乏 OTUD7B 会抑制与癌症进展、转移和代谢相关的信号通路。从机理上讲，OTUD7B可能通过WNT信号通路促进GC转移，特别是针对β-catenin：结论：OTUD7B是GC预后不良的新标志物，并能积极促进肿瘤转移。我们的研究结果揭示了OTUD7B调控的信号通路，并突出了治疗干预的潜在靶点。

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OTUD7B promotes cell migration and invasion, predicting poor prognosis of gastric cancer

Background

OTUD7B, a member of the ovarian tumor (OTU) protein superfamily, functions as a deubiquitinating enzyme and is associated with various biological processes and disease conditions, including tumors. In this study, we aimed to explore the expression patterns, prognostic significance, and the functional roles and underlying mechanisms of OTUD7B in gastric cancer (GC).

Materials and methods

Using a blend of bioinformatics, clinical case reviews, and molecular experiments, we evaluated the expression of OTUD7B in GC at both mRNA and protein levels. We examined the relationship between OTUD7B expression and clinicopathological characteristics of GC patients. Additionally, in vitro assays were utilized to assess the effects of OTUD7B on the migratory and invasive capabilities of GC cells. RNA sequencing analysis was conducted to identify critical genes and pathways linked to OTUD7B in GC.

Results

OTUD7B was found to be significantly overexpressed in GC, both at mRNA and protein levels. Higher levels of OTUD7B were positively associated with advanced tumor TNM stage, higher histological grade, and presence of lymph/vein invasion. These correlations were indicative of poorer overall survival (OS) and disease-free survival (DFS) in GC patients. In vitro assays revealed that genetic knockout of OTUD7B markedly reduced the migration and invasion of GC cells, while overexpression of OTUD7B led to enhanced cellular migration and invasion. Furthermore, RNA sequencing and bioinformatic analyses indicated that the absence of OTUD7B suppressed signaling pathways related to cancer progression, metastasis, and metabolism. Mechanistically, OTUD7B likely promotes GC metastasis through the WNT signaling pathway, specifically targeting β-catenin.

Conclusions

OTUD7B serves as a novel marker for poor prognosis in GC and actively promotes tumor metastasis. Our results shed light on the signaling pathways regulated by OTUD7B and highlight potential targets for therapeutic intervention.

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来源期刊

Pathology, research and practice 医学-病理学

CiteScore

5.00

自引率

3.60%

发文量

405

审稿时长

24 days

期刊介绍： Pathology, Research and Practice provides accessible coverage of the most recent developments across the entire field of pathology: Reviews focus on recent progress in pathology, while Comments look at interesting current problems and at hypotheses for future developments in pathology. Original Papers present novel findings on all aspects of general, anatomic and molecular pathology. Rapid Communications inform readers on preliminary findings that may be relevant for further studies and need to be communicated quickly. Teaching Cases look at new aspects or special diagnostic problems of diseases and at case reports relevant for the pathologist''s practice.