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接触蛋白1(CNTN1)通过早老素1(PSEN1)促进卵巢癌的细胞增殖和转移。

CNTN1 promotes cell proliferation and metastasis in ovarian cancer through PSEN1.

作者信息

Qi Zhiying, Ji Yuqing, Xu Yanying, Guo Ruimeng, Guo Xuewang, Dou Yu, Yue Yingying, Wang Fang

机构信息

Department of Gynecology, the Second Hospital of Tianjin Medical University, Tianjin, China.

Department of Gynecology, Tianjin Medical University, Tianjin, China.

出版信息

Transl Cancer Res. 2025 Jun 30;14(6):3690-3701. doi: 10.21037/tcr-2024-2234. Epub 2025 Jun 23.

DOI:10.21037/tcr-2024-2234
PMID:40687216
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12268885/
Abstract

BACKGROUND

Ovarian cancer (OC) is a commonly occurring malignant tumor in women with a high mortality rate. Early detection remains challenging, and therapeutic options for advanced OC are severely limited. Therefore, there is an urgent need to identify novel biomarkers and therapeutic targets to improve outcomes for patients. Contactin-1 (CNTN1), a member of the immunoglobulin superfamily, functions as a modulator of cancer progression, yet its specific role in OC remains undefined. The present study aimed to investigate the clinical significance and regulatory role of CNTN1 in OC proliferation and metastasis.

METHODS

This study examined CNTN1 expression in 40 paired OC tissue samples and cell lines using real-time quantitative reverse transcription polymerase chain reaction and immunohistochemistry. Colony formation assays assessed proliferative capacity, while transwell assays measured invasive and migratory potential. Additionally, a tumor xenograft model in nude mice was employed to verify in vivo proliferative effects.

RESULTS

The results demonstrated that CNTN1 expression was markedly elevated in OC tissues and positively associated with advanced tumor stage, metastasis, and poor prognosis. Silencing CNTN1 significantly inhibited proliferation, migration, and invasion in OC cell lines. Bioinformatics analysis combined with luciferase assays identified a regulatory interaction between CNTN1 and presenilin-1 (PSEN1), with CNTN1 expression positively correlating with PSEN1 levels in patient samples. Notably, PSEN1 overexpression reversed the impaired proliferation, migration, and invasion induced by CNTN1 suppression.

CONCLUSIONS

These findings suggest that CNTN1 promotes OC progression through PSEN1 regulation and may represent a prognostic biomarker for OC.

摘要

背景

卵巢癌(OC)是女性常见的恶性肿瘤,死亡率很高。早期检测仍然具有挑战性,晚期OC的治疗选择也极为有限。因此,迫切需要确定新的生物标志物和治疗靶点,以改善患者的治疗效果。Contactin-1(CNTN1)是免疫球蛋白超家族的成员,作为癌症进展的调节因子发挥作用,但其在OC中的具体作用仍不明确。本研究旨在探讨CNTN1在OC增殖和转移中的临床意义及调控作用。

方法

本研究采用实时定量逆转录聚合酶链反应和免疫组织化学方法,检测了40对OC组织样本和细胞系中CNTN1的表达。集落形成试验评估增殖能力,而Transwell试验测量侵袭和迁移潜力。此外,还采用裸鼠肿瘤异种移植模型验证体内增殖效应。

结果

结果表明,CNTN1在OC组织中的表达显著升高,且与肿瘤晚期、转移和预后不良呈正相关。沉默CNTN1可显著抑制OC细胞系的增殖、迁移和侵袭。生物信息学分析结合荧光素酶试验确定了CNTN1与早老素-1(PSEN1)之间的调控相互作用,患者样本中CNTN1表达与PSEN1水平呈正相关。值得注意的是,PSEN1过表达逆转了CNTN1抑制诱导的增殖、迁移和侵袭受损。

结论

这些发现表明,CNTN1通过调节PSEN1促进OC进展,可能是OC的一种预后生物标志物。

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本文引用的文献

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Identification of Contactin-1 as a Potential Biomarker and Therapeutic Target in Neuroblastoma.
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Targeting BRAF pathway in low-grade serous ovarian cancer.针对低级别浆液性卵巢癌中的 BRAF 通路。
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Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.2022 年全球癌症统计数据:全球 185 个国家和地区 36 种癌症的发病率和死亡率全球估计数。
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Key Molecules in Bladder Cancer Affect Patient Prognosis and Immunotherapy Efficacy: Further Exploration for and .膀胱癌相关关键分子影响患者预后及免疫治疗疗效: 和 的进一步探索
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MiR-654-3p Constrains Proliferation, Invasion, and Migration of Sinonasal Squamous Cell Carcinoma CREB1/PSEN1 Regulatory Axis.微小RNA-654-3p通过CREB1/PSEN1调控轴抑制鼻窦鳞状细胞癌的增殖、侵袭和迁移。
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Clinical Staging of Ovarian Cancer.卵巢癌的临床分期。
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miR-193a Directly Targets PSEN1 and Inhibits Gastric Cancer Cell Growth, the Activation of PI3K/Akt Signaling Pathway, and the Epithelial-to-Mesenchymal Transition.微小RNA-193a直接靶向早老素1并抑制胃癌细胞生长、PI3K/Akt信号通路的激活以及上皮-间质转化。
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Onco Targets Ther. 2021 Apr 19;14:2711-2726. doi: 10.2147/OTT.S280490. eCollection 2021.
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