Reduced Levels of miR-145-3p Drive Cell Cycle Progression in Advanced High-Grade Serous Ovarian Cancer

Sep 21, 2026

High-grade serous ovarian cancer (HGSOC) is highly lethal, with limited treatment options and an unfavorable prognosis. This work investigates how epigenetic mechanisms—including microRNAs (miRNAs) and DNA methylation—contribute to HGSOC progression. High-throughput profiling identified dysregulated miRNAs, with 20 differentially expressed and 11 validated by RT-qPCR. miR-145-3p was consistently downregulated after neoadjuvant therapy and distinguished tumors from controls. DNA methylation regulated MIR145 expression, and restoring miR-145-3p impaired migration and triggered G0/G1 arrest by modulating the cyclin D1-CDK4/6 pathway.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages20

Reading Time50 min

AccessFree to download

Introduction

Epigenetic regulation and miRNAs in HGSOC

Results

Dysregulated miRNAs in advanced-stage patients

miR-145-3p downregulation after neoadjuvant therapy

DNA methylation control of MIR145 expression

Functional effects on migration and cell cycle

Article Reduced Levels of miR-145-3p Drive Cell Cycle Progression in Advanced High-Grade Serous Ovarian Cancer Eva González-Cantó 1,†, Mariana Monteiro 2,†, Cristina Aghababyan 1,3, Ana Ferrero-Micó 4, Sergio Navarro-Serna 4, Maravillas Mellado-López 4, Sarai Tomás-Pérez 1, Juan Sandoval 5,6, Antoni Llueca 7,8,9, Alejandro Herreros-Pomares 10, Juan Gilabert-Estellés 1,3,11, Vicente Pérez-García 4,12, * and Josep Marí-Alexandre 1,13, * Citation: González-Cantó, E.; Monteiro, M.; Aghababyan, C.; Ferrero-Micó, A.; Navarro-Serna, S.; Mellado-López, M.; Tomás-Pérez, S.; Sandoval, J.; Llueca, A.; Herreros-Pomares, A.; et al. Reduced Levels of miR-145-3p Drive Cell Cycle Progression in Advanced High-Grade Serous Ovarian Cancer. Cells 2024, 13, 1904. [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)cells13221904 Academic Editors: Goberdhan P. Dimri and Yves St.-Pierre Received: 13 September 2024 Revised: 20 October 2024 Accepted: 8 November 2024 Published: 18 November 2024 Correction Statement: This article has been republished with a minor change. The change does not affect the scientific content of the article and further details are available within the backmatter of the website version of this article. Copyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) . 1 Research Laboratory in Biomarkers in Reproduction, Obstetrics and Gynecology, Research Foundation of the General University Hospital of Valencia, 46014 Valencia, Spain; [evagonzalezcanto@gmail.com](evagonzalezcanto@gmail.com) (E.G.-C.); [dra.kristina.agababyan@gmail.com](dra.kristina.agababyan@gmail.com) (C.A.); [sarai.altea@gmail.com](sarai.altea@gmail.com) (S.T.-P.); juangilaeste@yahoo.es (J.G.-E.) 2 Bioinformatics and Genomics Department, Saphetor SA, 1015 Lausanne, Switzerland; [marianabraga.m@gmail.com](marianabraga.m@gmail.com) 3 Department of Obstetrics and Gynecology, General University Hospital of Valencia Consortium, 46014 Valencia, Spain 4 Research Laboratory of Molecular Mechanisms of Placental Invasion, Centro de Investigación Príncipe Felipe, 46012 Valencia, Spain; [aferrero@cipf.es](aferrero@cipf.es) (A.F.-M.); [snavarro@cipf.es](snavarro@cipf.es) (S.N.-S.); [mmellado@cipf.es](mmellado@cipf.es) (M.M.-L.) 5 Epigenomics Unit, La Fe Health Research Institute, 46026 Valencia, Spain; epigenomica@iislafe.es 6 Biomarkers and Precision Medicine Unit (UByMP), La Fe Health Research Institute, 46026 Valencia, Spain 7 Department of Obstetrics and Gynecology, General University Hospital of Castellón, 12004 Castellón de la Plana, Spain; [antonillueca@gmail.com](antonillueca@gmail.com) 8 Multidisciplinary Unit of Abdominal Pelvic Oncology Surgery (MUAPOS), General University Hospital of Castellón, 12004 Castellón de la Plana, Spain 9 Department of Medicine, University Jaume I, 12006 Castellón de la Plana, Spain 10 Gynaecological Oncology Laboratory, Department of Oncology, KU Leuven, 3000 Leuven, Belgium; [alejandro.herrerospomares@kuleuven.be](alejandro.herrerospomares@kuleuven.be) 11 Department of Pediatrics, Obstetrics and Gynecology, University of Valencia, 46014 Valencia, Spain 12 Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas (CSIC), Universidad Autónoma de Madrid (UAM), 28049 Madrid, Spain 13 Department of Pathology, General University Hospital of Valencia Consortium, 46014 Valencia, Spain * Correspondence: vperez@cbm.csic.es (V.P.-G.); mari_josale@gva.es (J.M.-A.)† These authors contributed equally to this work. Abstract: High-grade serous ovarian cancer (HGSOC) is the most lethal form of gynecologic cancer, with limited treatment optio

FAQs

What epigenetic factors does the study focus on in HGSOC?

The study focuses on microRNAs (miRNAs) and DNA methylation as epigenetic regulators involved in HGSOC progression.

How was miR-145-3p identified and verified?

Comprehensive high-throughput analyses identified dysregulated miRNAs; miR-145-3p was among those validated by RT-qPCR in patient samples and cancer cell lines.

What functional changes occur when miR-145-3p is overexpressed?

Overexpression of miR-145-3p reduces cell migration and induces G0/G1 cell cycle arrest by modulating the cyclin D1-CDK4/6 pathway.

Sep 21, 2026

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