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Copine1 通过促进卵巢癌中 M2 巨噬细胞的激活来预测不良的临床结局。

Copine 1 predicts poor clinical outcomes by promoting M2 macrophage activation in ovarian cancer.

机构信息

Zhejiang Provincial Clinical Research Center for Obstetrics and Gynecology, Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325027, China.

出版信息

Carcinogenesis. 2023 Dec 15;44(10-11):748-759. doi: 10.1093/carcin/bgad067.

Abstract

OBJECTIVE

Copine 1 (CPNE1), a membrane-binding protein, influences the prognosis of various cancers. According to cBioPortal, CPNE1 amplification is a prevalent genetic mutation in ovarian cancer but with unknown oncogenic mechanism.

METHODS

This study analysed the CPNE1 expression in ovarian cancer using online datasets, as validated by immunohistochemistry (IHC), quantitative polymerase chain reaction (qPCR) and western blotting. Concurrently, the prognostic value of CPNE1 was accessed. Cell Counting Kit-8, colony formation, transwells and xenograft experiments were performed to evaluate the functions of CPNE1 during ovarian cancer carcinogenesis. CPNE1 and its related genes were analysed by g:Profiler and Tumour Immune Estimation Resource. Furthermore, human monocytic THP-1 cells were co-cultured with ES2 cells to investigate the effect of CPNE1 on macrophage polarization.

RESULTS

The results of bioinformatic analysis, IHC, qPCR and western blotting indicated a higher CPNE1 in ovarian cancer. CPNE1 overexpression demonstrated an association with a poor prognosis of ovarian cancer. Functionally, CPNE1 overexpression increased ES2 and SKOV3 cell proliferation, invasion and migration in vitro and promoted ovarian tumour xenograft growth in vivo, while CPNE1 knockdown led to opposite effects. Additionally, CPNE1 expression demonstrated an association with immune cell infiltration in ovarian cancer, especially macrophage. CPNE1 promoted protumour M2 macrophage polarization by upregulating cluster of differentiation 163 (CD163), CD206 and interleukin-10.

CONCLUSIONS

Our study revealed that CPNE1 mediated M2 macrophage polarization and provided a therapeutic target for ovarian cancer.

摘要

目的

膜结合蛋白 Copine1(CPNE1)影响多种癌症的预后。根据 cBioPortal,CPNE1 扩增是卵巢癌中一种常见的遗传突变,但致癌机制未知。

方法

本研究使用在线数据集分析了卵巢癌中 CPNE1 的表达,通过免疫组织化学(IHC)、定量聚合酶链反应(qPCR)和 Western blot 进行验证。同时,评估了 CPNE1 的预后价值。通过细胞计数试剂盒-8、集落形成、transwell 和异种移植实验评估 CPNE1 在卵巢癌发生过程中的功能。通过 g:Profiler 和肿瘤免疫估计资源分析 CPNE1 及其相关基因。此外,将人单核细胞 THP-1 细胞与 ES2 细胞共培养,研究 CPNE1 对巨噬细胞极化的影响。

结果

生物信息学分析、IHC、qPCR 和 Western blot 的结果表明卵巢癌中 CPNE1 水平较高。CPNE1 过表达与卵巢癌的不良预后相关。功能上,CPNE1 过表达增加了 ES2 和 SKOV3 细胞的体外增殖、侵袭和迁移,并促进了卵巢肿瘤异种移植的体内生长,而 CPNE1 敲低则导致相反的效果。此外,CPNE1 表达与卵巢癌中免疫细胞浸润有关,尤其是巨噬细胞。CPNE1 通过上调分化抗原 163(CD163)、CD206 和白细胞介素 10 促进促肿瘤 M2 巨噬细胞极化。

结论

本研究揭示了 CPNE1 介导的 M2 巨噬细胞极化,并为卵巢癌提供了一个治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8092/10773812/baf1ab0bef21/bgad067_fig7.jpg

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