Emerging roles of the Cancerous Inhibitor of Protein Phosphatase 2A (CIP2A) in ovarian cancer

Alice Filipe; Sayeh Saravi; Denis  Mustafov; Suzana  Panfilov; Simran Banger; Seyedehnajmeh Mousavikivaj; Maria Braoudaki; Sethikumar Kailasam; Yasser Riazalhosseini; Michelle A. Sahai; Fotios Drenos; Cristina  Sisu; Emmanouil Karteris

doi:10.1038/s41598-025-05013-0

Emerging roles of the Cancerous Inhibitor of Protein Phosphatase 2A (CIP2A) in ovarian cancer

Alice Filipe, Sayeh Saravi, Denis Mustafov, Suzana Panfilov, Simran Banger, Seyedehnajmeh Mousavikivaj, Maria Braoudaki, Sethikumar Kailasam, Yasser Riazalhosseini, Michelle A. Sahai, Fotios Drenos, Cristina Sisu, Emmanouil Karteris

Research output: Contribution to journal › Article › peer-review

Abstract

184,779 deaths worldwide. Cancerous Inhibitor of Phosphatase 2 A (CIP2A) is an oncoprotein and an endogenous inhibitor of PP2A. CIP2A is a key regulator for cellular processes (e.g. proliferation, DNA damage) and is involved in the progression of many malignancies. In this study we provide a comprehensive overview of its role in OvCa making use of in silico tools, clinical samples and in vitro models. CIP2A is overexpressed in OvCa patients, with metastatic patients having significantly higher expression when compared to patients with malignant and benign ovarian tumours. High CIP2A expression reduces both overall-and progression-free survival, whereas an R530T mutation is predicted
to cause structural destabilisation of the CIP2A dimer. We also provide evidence for microRNA (miRNA) and mRNA target interactions with CIP2A. Finally, we have studied the effects of CIP2A inhibition in an in vitro BRCA2 model compared to BRCA2 wild-type OvCa cells, using RNA-sequencing. Gene enrichment pointed towards changes p53 pathway, protein metabolism, and transporter activity,
DNA replication, and cell cycle. Our data provide a novel insight into the role of CIP2A in OvCa and the potential of drug repurposing for therapeutic interventions.

Original language	English
Article number	22382
Number of pages	15
Journal	Scientific Reports
Volume	15
DOIs	https://doi.org/10.1038/s41598-025-05013-0
Publication status	Published - 1 Jul 2025

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© The Author(s) 2025. This article is licensed under a Creative Commons Attribution 4.0 International License. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
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title = "Emerging roles of the Cancerous Inhibitor of Protein Phosphatase 2A (CIP2A) in ovarian cancer",

abstract = "184,779 deaths worldwide. Cancerous Inhibitor of Phosphatase 2 A (CIP2A) is an oncoprotein and an endogenous inhibitor of PP2A. CIP2A is a key regulator for cellular processes (e.g. proliferation, DNA damage) and is involved in the progression of many malignancies. In this study we provide a comprehensive overview of its role in OvCa making use of in silico tools, clinical samples and in vitro models. CIP2A is overexpressed in OvCa patients, with metastatic patients having significantly higher expression when compared to patients with malignant and benign ovarian tumours. High CIP2A expression reduces both overall-and progression-free survival, whereas an R530T mutation is predictedto cause structural destabilisation of the CIP2A dimer. We also provide evidence for microRNA (miRNA) and mRNA target interactions with CIP2A. Finally, we have studied the effects of CIP2A inhibition in an in vitro BRCA2 model compared to BRCA2 wild-type OvCa cells, using RNA-sequencing. Gene enrichment pointed towards changes p53 pathway, protein metabolism, and transporter activity,DNA replication, and cell cycle. Our data provide a novel insight into the role of CIP2A in OvCa and the potential of drug repurposing for therapeutic interventions.",

author = "Alice Filipe and Sayeh Saravi and Denis Mustafov and Suzana Panfilov and Simran Banger and Seyedehnajmeh Mousavikivaj and Maria Braoudaki and Sethikumar Kailasam and Yasser Riazalhosseini and Sahai, {Michelle A.} and Fotios Drenos and Cristina Sisu and Emmanouil Karteris",

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AU - Filipe, Alice

AU - Saravi, Sayeh

AU - Mustafov, Denis

AU - Panfilov, Suzana

AU - Banger, Simran

AU - Mousavikivaj, Seyedehnajmeh

AU - Braoudaki, Maria

AU - Kailasam, Sethikumar

AU - Riazalhosseini, Yasser

AU - Sahai, Michelle A.

AU - Drenos, Fotios

AU - Sisu, Cristina

AU - Karteris, Emmanouil

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PY - 2025/7/1

Y1 - 2025/7/1

N2 - 184,779 deaths worldwide. Cancerous Inhibitor of Phosphatase 2 A (CIP2A) is an oncoprotein and an endogenous inhibitor of PP2A. CIP2A is a key regulator for cellular processes (e.g. proliferation, DNA damage) and is involved in the progression of many malignancies. In this study we provide a comprehensive overview of its role in OvCa making use of in silico tools, clinical samples and in vitro models. CIP2A is overexpressed in OvCa patients, with metastatic patients having significantly higher expression when compared to patients with malignant and benign ovarian tumours. High CIP2A expression reduces both overall-and progression-free survival, whereas an R530T mutation is predictedto cause structural destabilisation of the CIP2A dimer. We also provide evidence for microRNA (miRNA) and mRNA target interactions with CIP2A. Finally, we have studied the effects of CIP2A inhibition in an in vitro BRCA2 model compared to BRCA2 wild-type OvCa cells, using RNA-sequencing. Gene enrichment pointed towards changes p53 pathway, protein metabolism, and transporter activity,DNA replication, and cell cycle. Our data provide a novel insight into the role of CIP2A in OvCa and the potential of drug repurposing for therapeutic interventions.

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Emerging roles of the Cancerous Inhibitor of Protein Phosphatase 2A (CIP2A) in ovarian cancer

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