Reduced Levels of miR-145-3p Drive Cell Cycle Progression in Advanced High-Grade Serous Ovarian Cancer
High-grade serous ovarian cancer (HGSOC) is the most lethal form of gynecologic cancer, with limited treatment options and a poor prognosis. Epigenetic factors, such as microRNAs (miRNAs) and DNA methylation, play pivotal roles in cancer progression, yet their specific contributions to HGSOC remain...
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MDPI AG
2024-11-01
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| author | Eva González-Cantó Mariana Monteiro Cristina Aghababyan Ana Ferrero-Micó Sergio Navarro-Serna Maravillas Mellado-López Sarai Tomás-Pérez Juan Sandoval Antoni Llueca Alejandro Herreros-Pomares Juan Gilabert-Estellés Vicente Pérez-García Josep Marí-Alexandre |
| author_facet | Eva González-Cantó Mariana Monteiro Cristina Aghababyan Ana Ferrero-Micó Sergio Navarro-Serna Maravillas Mellado-López Sarai Tomás-Pérez Juan Sandoval Antoni Llueca Alejandro Herreros-Pomares Juan Gilabert-Estellés Vicente Pérez-García Josep Marí-Alexandre |
| author_sort | Eva González-Cantó |
| collection | DOAJ |
| description | High-grade serous ovarian cancer (HGSOC) is the most lethal form of gynecologic cancer, with limited treatment options and a poor prognosis. Epigenetic factors, such as microRNAs (miRNAs) and DNA methylation, play pivotal roles in cancer progression, yet their specific contributions to HGSOC remain insufficiently understood. In this study, we performed comprehensive high-throughput analyses to identify dysregulated miRNAs in HGSOC and investigate their epigenetic regulation. Analysis of tissue samples from advanced-stage HGSOC patients revealed 20 differentially expressed miRNAs, 11 of which were corroborated via RT-qPCR in patient samples and cancer cell lines. Among these, miR-145-3p was consistently downregulated post-neoadjuvant therapy and was able to distinguish tumoural from control tissues. Further investigation confirmed that DNA methylation controls <i>MIR145</i> expression. Functional assays showed that overexpression of miR-145-3p significantly reduced cell migration and induced G0/G1 cell cycle arrest by modulating the cyclin D1-CDK4/6 pathway. These findings suggest that miR-145-3p downregulation enhances cell proliferation and motility in HGSOC, implicating its restoration as a potential therapeutic target focused on G1/S phase regulation in the treatment of HGSOC. |
| format | Article |
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| institution | OA Journals |
| issn | 2073-4409 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | MDPI AG |
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| series | Cells |
| spelling | doaj-art-41ede39d510c449ebd10ceefacf536d52025-08-20T02:08:09ZengMDPI AGCells2073-44092024-11-011322190410.3390/cells13221904Reduced Levels of miR-145-3p Drive Cell Cycle Progression in Advanced High-Grade Serous Ovarian CancerEva González-Cantó0Mariana Monteiro1Cristina Aghababyan2Ana Ferrero-Micó3Sergio Navarro-Serna4Maravillas Mellado-López5Sarai Tomás-Pérez6Juan Sandoval7Antoni Llueca8Alejandro Herreros-Pomares9Juan Gilabert-Estellés10Vicente Pérez-García11Josep Marí-Alexandre12Research Laboratory in Biomarkers in Reproduction, Obstetrics and Gynecology, Research Foundation of the General University Hospital of Valencia, 46014 Valencia, SpainBioinformatics and Genomics Department, Saphetor SA, 1015 Lausanne, SwitzerlandResearch Laboratory in Biomarkers in Reproduction, Obstetrics and Gynecology, Research Foundation of the General University Hospital of Valencia, 46014 Valencia, SpainResearch Laboratory of Molecular Mechanisms of Placental Invasion, Centro de Investigación Príncipe Felipe, 46012 Valencia, SpainResearch Laboratory of Molecular Mechanisms of Placental Invasion, Centro de Investigación Príncipe Felipe, 46012 Valencia, SpainResearch Laboratory of Molecular Mechanisms of Placental Invasion, Centro de Investigación Príncipe Felipe, 46012 Valencia, SpainResearch Laboratory in Biomarkers in Reproduction, Obstetrics and Gynecology, Research Foundation of the General University Hospital of Valencia, 46014 Valencia, SpainEpigenomics Unit, La Fe Health Research Institute, 46026 Valencia, SpainDepartment of Obstetrics and Gynecology, General University Hospital of Castellón, 12004 Castellón de la Plana, SpainGynaecological Oncology Laboratory, Department of Oncology, KU Leuven, 3000 Leuven, BelgiumResearch Laboratory in Biomarkers in Reproduction, Obstetrics and Gynecology, Research Foundation of the General University Hospital of Valencia, 46014 Valencia, SpainResearch Laboratory of Molecular Mechanisms of Placental Invasion, Centro de Investigación Príncipe Felipe, 46012 Valencia, SpainResearch Laboratory in Biomarkers in Reproduction, Obstetrics and Gynecology, Research Foundation of the General University Hospital of Valencia, 46014 Valencia, SpainHigh-grade serous ovarian cancer (HGSOC) is the most lethal form of gynecologic cancer, with limited treatment options and a poor prognosis. Epigenetic factors, such as microRNAs (miRNAs) and DNA methylation, play pivotal roles in cancer progression, yet their specific contributions to HGSOC remain insufficiently understood. In this study, we performed comprehensive high-throughput analyses to identify dysregulated miRNAs in HGSOC and investigate their epigenetic regulation. Analysis of tissue samples from advanced-stage HGSOC patients revealed 20 differentially expressed miRNAs, 11 of which were corroborated via RT-qPCR in patient samples and cancer cell lines. Among these, miR-145-3p was consistently downregulated post-neoadjuvant therapy and was able to distinguish tumoural from control tissues. Further investigation confirmed that DNA methylation controls <i>MIR145</i> expression. Functional assays showed that overexpression of miR-145-3p significantly reduced cell migration and induced G0/G1 cell cycle arrest by modulating the cyclin D1-CDK4/6 pathway. These findings suggest that miR-145-3p downregulation enhances cell proliferation and motility in HGSOC, implicating its restoration as a potential therapeutic target focused on G1/S phase regulation in the treatment of HGSOC.https://www.mdpi.com/2073-4409/13/22/1904high-grade serous ovarian cancermiRNAsDNA methylationmiR-145-3pcell cycle proliferationcyclin D1-CDK4/6 pathway |
| spellingShingle | Eva González-Cantó Mariana Monteiro Cristina Aghababyan Ana Ferrero-Micó Sergio Navarro-Serna Maravillas Mellado-López Sarai Tomás-Pérez Juan Sandoval Antoni Llueca Alejandro Herreros-Pomares Juan Gilabert-Estellés Vicente Pérez-García Josep Marí-Alexandre Reduced Levels of miR-145-3p Drive Cell Cycle Progression in Advanced High-Grade Serous Ovarian Cancer Cells high-grade serous ovarian cancer miRNAs DNA methylation miR-145-3p cell cycle proliferation cyclin D1-CDK4/6 pathway |
| title | Reduced Levels of miR-145-3p Drive Cell Cycle Progression in Advanced High-Grade Serous Ovarian Cancer |
| title_full | Reduced Levels of miR-145-3p Drive Cell Cycle Progression in Advanced High-Grade Serous Ovarian Cancer |
| title_fullStr | Reduced Levels of miR-145-3p Drive Cell Cycle Progression in Advanced High-Grade Serous Ovarian Cancer |
| title_full_unstemmed | Reduced Levels of miR-145-3p Drive Cell Cycle Progression in Advanced High-Grade Serous Ovarian Cancer |
| title_short | Reduced Levels of miR-145-3p Drive Cell Cycle Progression in Advanced High-Grade Serous Ovarian Cancer |
| title_sort | reduced levels of mir 145 3p drive cell cycle progression in advanced high grade serous ovarian cancer |
| topic | high-grade serous ovarian cancer miRNAs DNA methylation miR-145-3p cell cycle proliferation cyclin D1-CDK4/6 pathway |
| url | https://www.mdpi.com/2073-4409/13/22/1904 |
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