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Article

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

by
Eleni Anastasiadou
1,*,
Elena Messina
1,
Tiziana Sanavia
2,
Lucia Mundo
3,4,
Federica Farinella
1,
Stefano Lazzi
3,
Francesca Megiorni
1,
Simona Ceccarelli
1,
Paola Pontecorvi
1,
Francesco Marampon
5,
Cira Rosaria Tiziana Di Gioia
6,
Giorgia Perniola
7,
Pierluigi Benedetti Panici
7,
Lorenzo Leoncini
3,
Pankaj Trivedi
1,
Andrea Lenzi
1 and
Cinzia Marchese
1
1
Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, Italy
2
Department of Medical Sciences, University of Torino, 10126 Torino, Italy
3
Department of Medical Biotechnology, Section of Pathology, University of Siena, 53100 Siena, Italy
4
Health Research Institute, University of Limerick, Limerick V94 T9PX, Ireland
5
Department of Radiotherapy, Policlinico Umberto I, Sapienza University of Rome, 00161 Rome, Italy
6
Department of Radiological, Oncological and Pathological Sciences, Sapienza University of Rome, 00161 Rome, Italy
7
Department of Gynecological-Obstetric Sciences and Urological Sciences, Sapienza University of Rome, 00161 Rome, Italy
*
Author to whom correspondence should be addressed.
Cells 2021, 10(3), 519; https://doi.org/10.3390/cells10030519
Submission received: 20 January 2021 / Revised: 22 February 2021 / Accepted: 24 February 2021 / Published: 1 March 2021
(This article belongs to the Collection Targeting Signal Transduction Pathways and Non-coding RNAs as Potential Therapy in Cancer and Aging)
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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 β-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 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.
Keywords: epithelial ovarian cancer; immune checkpoints; PARPi; ionizing radiation; miRNA-based therapy epithelial ovarian cancer; immune checkpoints; PARPi; ionizing radiation; miRNA-based therapy

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MDPI and ACS Style

Anastasiadou, E.; Messina, E.; Sanavia, T.; Mundo, L.; Farinella, F.; Lazzi, S.; Megiorni, F.; Ceccarelli, S.; Pontecorvi, P.; Marampon, F.; et al. 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. Cells 2021, 10, 519. https://doi.org/10.3390/cells10030519

AMA Style

Anastasiadou E, Messina E, Sanavia T, Mundo L, Farinella F, Lazzi S, Megiorni F, Ceccarelli S, Pontecorvi P, Marampon F, et al. 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. Cells. 2021; 10(3):519. https://doi.org/10.3390/cells10030519

Chicago/Turabian Style

Anastasiadou, Eleni, Elena Messina, Tiziana Sanavia, Lucia Mundo, Federica Farinella, Stefano Lazzi, Francesca Megiorni, Simona Ceccarelli, Paola Pontecorvi, Francesco Marampon, and et al. 2021. "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" Cells 10, no. 3: 519. https://doi.org/10.3390/cells10030519

APA Style

Anastasiadou, E., Messina, E., Sanavia, T., Mundo, L., Farinella, F., Lazzi, S., Megiorni, F., Ceccarelli, S., Pontecorvi, P., Marampon, F., Di Gioia, C. R. T., Perniola, G., Panici, P. B., Leoncini, L., Trivedi, P., Lenzi, A., & Marchese, C. (2021). 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. Cells, 10(3), 519. https://doi.org/10.3390/cells10030519

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