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MiR-200c-3p contrasts PD-L1 induction by combinatorial therapies and slows proliferation of epithelial ovarian cancer through downregulation of β-catenin and c-myc

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dc.contributor.author Anastasiadou, Eleni
dc.contributor.author Messina, Elena
dc.contributor.author Sanavia, Tiziana
dc.contributor.author Mundo, Lucia
dc.contributor.author Farinella, Federica
dc.contributor.author Lazzi, Stefano
dc.contributor.author Megiorni, Francesca
dc.contributor.author Ceccarelli, Simona
dc.contributor.author Pontecorvi, Paola
dc.contributor.author Marampon, Francesco
dc.contributor.author Di Gioia, Cira Rosaria Tiziana
dc.contributor.author Perniola, Giorgia
dc.contributor.author Panici, Pierluigi Benedetti
dc.contributor.author Leoncini, Lorenzo
dc.contributor.author Trivedi, Pankaj
dc.contributor.author Lenzi, Andrea
dc.contributor.author Marchese, Cinzia
dc.date.accessioned 2021-03-24T12:02:14Z
dc.date.available 2021-03-24T12:02:14Z
dc.date.issued 2021
dc.identifier.uri http://hdl.handle.net/10344/9912
dc.description peer-reviewed en_US
dc.description.abstract Conventional/targeted chemotherapies and ionizing radiation (IR) are being used both as monotherapies and in combination for the treatment of epithelial ovarian cancer (EOC). Several studies show that these therapies might favor oncogenic signaling and impede anti-tumor responses. MiR-200c is considered a master regulator of EOC-related oncogenes. In this study, we sought to investigate if chemotherapy and IR could influence the expression of miR-200c-3p and its target genes, like the immune checkpoint PD-L1 and other oncogenes in a cohort of EOC patients’ biopsies. Indeed, PD-L1 expression was induced, while miR-200c-3p was significantly reduced in these biopsies posttherapy. The effect of miR-200c-3p target genes was assessed in miR-200c transfected SKOV3 cells untreated and treated with olaparib and IR alone. Under all experimental conditions, miR-200c-3p concomitantly reduced PD-L1, c-Myc and β-catenin expression and sensitized ovarian cancer cells to olaparib and irradiation. In silico analyses further confirmed the anti-correlation between miR-200c3p with c-Myc and β-catenin in 46 OC cell lines and showed that a higher miR-200c-3p expression associates with a less tumorigenic microenvironment. These findings provide new insights into how miR-200c-3p could be used to hold in check the adverse effects of conventional chemotherapy, targeted therapy and radiation therapy, and offer a novel therapeutic strategy for EOC. en_US
dc.language.iso eng en_US
dc.publisher MDPI en_US
dc.relation.ispartofseries Cells;10, 519
dc.subject epithelial ovarian cancer en_US
dc.title MiR-200c-3p contrasts PD-L1 induction by combinatorial therapies and slows proliferation of epithelial ovarian cancer through downregulation of β-catenin and c-myc en_US
dc.type info:eu-repo/semantics/article en_US
dc.type.supercollection all_ul_research en_US
dc.type.supercollection ul_published_reviewed en_US
dc.identifier.doi 10.3390/cells10030519
dc.rights.accessrights info:eu-repo/semantics/openAccess en_US


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