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 post-therapy. 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 beta-catenin expression and sensitized ovarian cancer cells to olaparib and irradiation. In silico analyses further confirmed the anti-correlation between miR-200c-3p with c-Myc and beta-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.

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 / Anastasiadou, Eleni; Messina, Elena; Sanavia, Tiziana; Mundo, Lucia; Farinella, Federica; Lazzi, Stefano; Megiorni, Francesca; Ceccarelli, Simona; Pontecorvi, Paola; Marampon, Francesco; Di Gioia, Cira Rosaria Tiziana; Perniola, Giorgia; Panici, Pierluigi Benedetti; Leoncini, Lorenzo; Trivedi, Pankaj; Lenzi, Andrea; Marchese, Cinzia. - In: CELLS. - ISSN 2073-4409. - 10:3(2021), pp. 1-21. [10.3390/cells10030519]

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

Anastasiadou, Eleni
Primo
;
Messina, Elena
Secondo
;
Megiorni, Francesca;Ceccarelli, Simona;Pontecorvi, Paola;Marampon, Francesco;Di Gioia, Cira Rosaria Tiziana;Perniola, Giorgia;Panici, Pierluigi Benedetti;Trivedi, Pankaj;Lenzi, Andrea
Penultimo
;
Marchese, Cinzia
Ultimo
2021

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 post-therapy. 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 beta-catenin expression and sensitized ovarian cancer cells to olaparib and irradiation. In silico analyses further confirmed the anti-correlation between miR-200c-3p with c-Myc and beta-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.
2021
PARPi; epithelial ovarian cancer; immune checkpoints; ionizing radiation; miRNA-based therapy
01 Pubblicazione su rivista::01a Articolo in rivista
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 / Anastasiadou, Eleni; Messina, Elena; Sanavia, Tiziana; Mundo, Lucia; Farinella, Federica; Lazzi, Stefano; Megiorni, Francesca; Ceccarelli, Simona; Pontecorvi, Paola; Marampon, Francesco; Di Gioia, Cira Rosaria Tiziana; Perniola, Giorgia; Panici, Pierluigi Benedetti; Leoncini, Lorenzo; Trivedi, Pankaj; Lenzi, Andrea; Marchese, Cinzia. - In: CELLS. - ISSN 2073-4409. - 10:3(2021), pp. 1-21. [10.3390/cells10030519]
File allegati a questo prodotto
File Dimensione Formato  
Anastasiadou _MiR-200c-3p_2021.pdf

accesso aperto

Note: https://www.mdpi.com/2073-4409/10/3/519
Tipologia: Versione editoriale (versione pubblicata con il layout dell'editore)
Licenza: Creative commons
Dimensione 2.03 MB
Formato Adobe PDF
2.03 MB Adobe PDF

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1530106
Citazioni
  • ???jsp.display-item.citation.pmc??? 10
  • Scopus 19
  • ???jsp.display-item.citation.isi??? 19
social impact