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脂肪细胞来源的CCDC3通过Wnt/β-连环蛋白信号通路促进上皮性卵巢癌的肿瘤发生。

Adipocyte-derived CCDC3 promotes tumorigenesis in epithelial ovarian cancer through the Wnt/ß-catenin signalling pathway.

作者信息

Wang Fen, Jin Feng, Peng Shanshan, Li Chen, Wang Li, Wang Shubin

机构信息

Department of Medical Oncology, Peking University Shenzhen Hospital, Shenzhen Key Laboratory of Gastrointestinal Cancer Translational Research, Cancer Institute of Shenzhen-PKU-HKUST Medical Center, Shenzhen 518036, China.

Department of Gynecology, Shenzhen Baoan Maternal and Child Healthcare Hospital, Shenzhen 518000, China.

出版信息

Biochem Biophys Rep. 2023 Jul 12;35:101507. doi: 10.1016/j.bbrep.2023.101507. eCollection 2023 Sep.

DOI:10.1016/j.bbrep.2023.101507
PMID:37601453
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10439399/
Abstract

INTRODUCTION

Epithelial ovarian cancer (EOC) is a highly aggressive disease whose unique metastatic site is the omentum. Coiled-coil domain containing 3 (CCDC3) is an adipocyte-derived secreted protein that is specifically elevated in omental adipose tissue. However, its function is still unknown.

MATERIAL AND METHODS

Initially, a Kaplan-Meier plot was applied to evaluate the prognostic value of CCDC3 expression in patients with EOC. A bioinformatics analysis was next used to explore the biological function of CCDC3 in EOC. Western blot, quantitative real-time polymerase chain reaction, and invasion and migration assays were performed using SKOV3 cells and CCDC3 secreted by rat adipocytes to analyzes the impact of CCDC3 on EOC and the underlying mechanism.

RESULTS

Overexpression of CCDC3 was associated with poor prognosis of EOC. CCDC3 interacted with multiple key signalling pathways, including the Wnt/β-catenin pathway. EOC cellular proliferation, migration, and invasion were promoted when co-cultured with CCDC3 enriched conditioned medium, and this tumour-promoting effect was induced by activating the Wnt/β-catenin pathway. Furthermore, the epithelial-mesenchymal transition of EOC cells was reversed after silencing.

CONCLUSIONS

Our results support that CCDC3 promotes EOC tumorigenesis through the Wnt/β-catenin pathway and that CCDC3 may serve as a novel prognostic biomarker and therapeutic target for metastatic EOC.

摘要

引言

上皮性卵巢癌(EOC)是一种侵袭性很强的疾病,其独特的转移部位是大网膜。卷曲螺旋结构域包含蛋白3(CCDC3)是一种脂肪细胞衍生的分泌蛋白,在大网膜脂肪组织中特异性升高。然而,其功能仍不清楚。

材料与方法

首先,应用Kaplan-Meier曲线评估CCDC3表达在EOC患者中的预后价值。接下来使用生物信息学分析来探索CCDC3在EOC中的生物学功能。使用SKOV3细胞和大鼠脂肪细胞分泌的CCDC3进行蛋白质免疫印迹、定量实时聚合酶链反应以及侵袭和迁移实验,以分析CCDC3对EOC的影响及其潜在机制。

结果

CCDC3的过表达与EOC的不良预后相关。CCDC3与多个关键信号通路相互作用,包括Wnt/β-连环蛋白通路。与富含CCDC3的条件培养基共培养时,EOC细胞的增殖、迁移和侵袭得到促进,并且这种促肿瘤作用是通过激活Wnt/β-连环蛋白通路诱导的。此外,沉默后EOC细胞的上皮-间质转化被逆转。

结论

我们的结果支持CCDC3通过Wnt/β-连环蛋白通路促进EOC肿瘤发生,并且CCDC3可能作为转移性EOC的一种新的预后生物标志物和治疗靶点。

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