PTTG1 promotes M2 macrophage polarization via the cGMP-PKG signaling pathway and facilitates EMT progression in human epithelial ovarian cancer cells

Abstract Epithelial Ovarian Cancer (EOC) is complex and heterogeneous, making accurate prognosis and treatment prediction difficult. New therapeutic targets and their mechanisms are urgently needed. This study explored the role of PTTG1 in ovarian cancer via the cGMP-PKG signaling pathway, focusing...

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Main Authors: Liang Tian, Liyun Liu, Chunlou Wang, Yan Kong, Zhigang Miao, Qing Yao, He Zhang, Yuehong Li
Format: Article
Language:English
Published: Springer 2025-05-01
Series:Discover Oncology
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Online Access:https://doi.org/10.1007/s12672-025-02512-4
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author Liang Tian
Liyun Liu
Chunlou Wang
Yan Kong
Zhigang Miao
Qing Yao
He Zhang
Yuehong Li
author_facet Liang Tian
Liyun Liu
Chunlou Wang
Yan Kong
Zhigang Miao
Qing Yao
He Zhang
Yuehong Li
author_sort Liang Tian
collection DOAJ
description Abstract Epithelial Ovarian Cancer (EOC) is complex and heterogeneous, making accurate prognosis and treatment prediction difficult. New therapeutic targets and their mechanisms are urgently needed. This study explored the role of PTTG1 in ovarian cancer via the cGMP-PKG signaling pathway, focusing on its effects on M2 macrophage polarization and EMT progression in EOC cells. Using the GSE135886 database, we performed differential gene expression, pathway enrichment, and immune infiltration analyses to identify key targets influencing EMT and macrophage polarization. We then constructed PTTG1 knockdown and overexpression cell lines to assess the impact of PTTG1 on cell proliferation, migration, invasion, EMT, and macrophage polarization in vitro. Analysis revealed that differentially expressed genes were enriched in the cGMP-PKG pathway and correlated with M2 macrophages. PTTG1 overexpression in A2780 and SK-OV-3 ovarian cancer cells promoted proliferation, invasion, and migration, while enhancing sGC, PKG1, and PKG2 expression to activate the cGMP-PKG pathway and induce M2 macrophage polarization. PTTG1 knockdown produced opposite results, reinforcing our conclusions. This study uncovers a novel mechanism of PTTG1 in ovarian cancer development and suggests it as a potential therapeutic target.
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institution Kabale University
issn 2730-6011
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publishDate 2025-05-01
publisher Springer
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series Discover Oncology
spelling doaj-art-5d022ffe4ad644a48de1679c7b6112ce2025-08-20T03:53:57ZengSpringerDiscover Oncology2730-60112025-05-0116111710.1007/s12672-025-02512-4PTTG1 promotes M2 macrophage polarization via the cGMP-PKG signaling pathway and facilitates EMT progression in human epithelial ovarian cancer cellsLiang Tian0Liyun Liu1Chunlou Wang2Yan Kong3Zhigang Miao4Qing Yao5He Zhang6Yuehong Li7Department of Pathology, The Second Hospital of Hebei Medical UniversityDepartment of Pathology, Tangshan Gongren HospitalDepartment of Pathology, Cangzhou Central HospitalDepartment of Clinical Lab, Cangzhou Central HospitalDepartment of Pathology, Cangzhou Central HospitalDepartment of Pathology, Cangzhou Central HospitalDepartment of Pathology, Cangzhou Central HospitalDepartment of Pathology, The Second Hospital of Hebei Medical UniversityAbstract Epithelial Ovarian Cancer (EOC) is complex and heterogeneous, making accurate prognosis and treatment prediction difficult. New therapeutic targets and their mechanisms are urgently needed. This study explored the role of PTTG1 in ovarian cancer via the cGMP-PKG signaling pathway, focusing on its effects on M2 macrophage polarization and EMT progression in EOC cells. Using the GSE135886 database, we performed differential gene expression, pathway enrichment, and immune infiltration analyses to identify key targets influencing EMT and macrophage polarization. We then constructed PTTG1 knockdown and overexpression cell lines to assess the impact of PTTG1 on cell proliferation, migration, invasion, EMT, and macrophage polarization in vitro. Analysis revealed that differentially expressed genes were enriched in the cGMP-PKG pathway and correlated with M2 macrophages. PTTG1 overexpression in A2780 and SK-OV-3 ovarian cancer cells promoted proliferation, invasion, and migration, while enhancing sGC, PKG1, and PKG2 expression to activate the cGMP-PKG pathway and induce M2 macrophage polarization. PTTG1 knockdown produced opposite results, reinforcing our conclusions. This study uncovers a novel mechanism of PTTG1 in ovarian cancer development and suggests it as a potential therapeutic target.https://doi.org/10.1007/s12672-025-02512-4Ovarian cancerPTTG1CGMP-PKG signaling pathwayMacrophage polarizationEpithelial-mesenchymal transition
spellingShingle Liang Tian
Liyun Liu
Chunlou Wang
Yan Kong
Zhigang Miao
Qing Yao
He Zhang
Yuehong Li
PTTG1 promotes M2 macrophage polarization via the cGMP-PKG signaling pathway and facilitates EMT progression in human epithelial ovarian cancer cells
Discover Oncology
Ovarian cancer
PTTG1
CGMP-PKG signaling pathway
Macrophage polarization
Epithelial-mesenchymal transition
title PTTG1 promotes M2 macrophage polarization via the cGMP-PKG signaling pathway and facilitates EMT progression in human epithelial ovarian cancer cells
title_full PTTG1 promotes M2 macrophage polarization via the cGMP-PKG signaling pathway and facilitates EMT progression in human epithelial ovarian cancer cells
title_fullStr PTTG1 promotes M2 macrophage polarization via the cGMP-PKG signaling pathway and facilitates EMT progression in human epithelial ovarian cancer cells
title_full_unstemmed PTTG1 promotes M2 macrophage polarization via the cGMP-PKG signaling pathway and facilitates EMT progression in human epithelial ovarian cancer cells
title_short PTTG1 promotes M2 macrophage polarization via the cGMP-PKG signaling pathway and facilitates EMT progression in human epithelial ovarian cancer cells
title_sort pttg1 promotes m2 macrophage polarization via the cgmp pkg signaling pathway and facilitates emt progression in human epithelial ovarian cancer cells
topic Ovarian cancer
PTTG1
CGMP-PKG signaling pathway
Macrophage polarization
Epithelial-mesenchymal transition
url https://doi.org/10.1007/s12672-025-02512-4
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