Calcineurin Gamma Catalytic Subunit PPP3CC Inhibition by miR-200c-3p Affects Apoptosis in Epithelial Ovarian Cancer
Epithelial ovarian cancer (EOC) outpaces all the other forms of the female reproductive system malignancies. MicroRNAs have emerged as promising predictive biomarkers to therapeutic treatments as their expression might characterize the tumor stage or grade. In EOC, miR-200c is considered a master re...
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doaj-566012973ee14c7aa85dc7fbf68b29eb2021-09-26T00:13:23ZengMDPI AGGenes2073-44252021-09-01121400140010.3390/genes12091400Calcineurin Gamma Catalytic Subunit PPP3CC Inhibition by miR-200c-3p Affects Apoptosis in Epithelial Ovarian CancerEleni Anastasiadou0Elena Messina1Tiziana Sanavia2Vittorio Labruna3Simona Ceccarelli4Francesca Megiorni5Giulia Gerini6Paola Pontecorvi7Simona Camero8Giorgia Perniola9Mary Anna Venneri10Pankaj Trivedi11Andrea Lenzi12Cinzia Marchese13Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, ItalyDepartment of Experimental Medicine, Sapienza University of Rome, 00161 Rome, ItalyDepartment of Medical Sciences, University of Torino, 10126 Torino, ItalyDepartment of Experimental Medicine, Sapienza University of Rome, 00161 Rome, ItalyDepartment of Experimental Medicine, Sapienza University of Rome, 00161 Rome, ItalyDepartment of Experimental Medicine, Sapienza University of Rome, 00161 Rome, ItalyDepartment of Experimental Medicine, Sapienza University of Rome, 00161 Rome, ItalyDepartment of Experimental Medicine, Sapienza University of Rome, 00161 Rome, ItalyDepartment of Maternal, Infantile and Urological Sciences, “Sapienza” University of Rome, 00161 Rome, ItalyDepartment of Gynecological-Obstetric Sciences and Urological Sciences, Sapienza University of Rome, 00161 Rome, ItalyDepartment of Experimental Medicine, Sapienza University of Rome, 00161 Rome, ItalyDepartment of Experimental Medicine, Sapienza University of Rome, 00161 Rome, ItalyDepartment of Experimental Medicine, Sapienza University of Rome, 00161 Rome, ItalyDepartment of Experimental Medicine, Sapienza University of Rome, 00161 Rome, ItalyEpithelial ovarian cancer (EOC) outpaces all the other forms of the female reproductive system malignancies. MicroRNAs have emerged as promising predictive biomarkers to therapeutic treatments as their expression might characterize the tumor stage or grade. In EOC, miR-200c is considered a master regulator of oncogenes or tumor suppressors. To investigate novel miR-200c-3p target genes involved in EOC tumorigenesis, we evaluated the association between this miRNA and the mRNA expression of several potential target genes by RNA-seq data of both 46 EOC cell lines from Cancer Cell line Encyclopedia (CCLE) and 456 EOC patient bio-specimens from The Cancer Genome Atlas (TCGA). Both analyses showed a significant anticorrelation between miR-200c-3p and the protein phosphatase 3 catalytic subunit γ of calcineurin (PPP3CC) levels involved in the apoptosis pathway. Quantitative mRNA expression analysis in patient biopsies confirmed the inverse correlation between miR-200c-3p and PPP3CC levels. In vitro regulation of PPP3CC expression through miR-200c-3p and RNA interference technology led to a concomitant modulation of BCL2- and p-AKT-related pathways, suggesting the tumor suppressive role of PPP3CC in EOC. Our results suggest that inhibition of high expression of miR-200c-3p in EOC might lead to overexpression of the tumor suppressor PPP3CC and subsequent induction of apoptosis in EOC patients.https://www.mdpi.com/2073-4425/12/9/1400epithelial ovarian cancermiRNAPPP3CCcalcineurinapoptosisTCGA and CCLE databases |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Eleni Anastasiadou Elena Messina Tiziana Sanavia Vittorio Labruna Simona Ceccarelli Francesca Megiorni Giulia Gerini Paola Pontecorvi Simona Camero Giorgia Perniola Mary Anna Venneri Pankaj Trivedi Andrea Lenzi Cinzia Marchese |
spellingShingle |
Eleni Anastasiadou Elena Messina Tiziana Sanavia Vittorio Labruna Simona Ceccarelli Francesca Megiorni Giulia Gerini Paola Pontecorvi Simona Camero Giorgia Perniola Mary Anna Venneri Pankaj Trivedi Andrea Lenzi Cinzia Marchese Calcineurin Gamma Catalytic Subunit PPP3CC Inhibition by miR-200c-3p Affects Apoptosis in Epithelial Ovarian Cancer Genes epithelial ovarian cancer miRNA PPP3CC calcineurin apoptosis TCGA and CCLE databases |
author_facet |
Eleni Anastasiadou Elena Messina Tiziana Sanavia Vittorio Labruna Simona Ceccarelli Francesca Megiorni Giulia Gerini Paola Pontecorvi Simona Camero Giorgia Perniola Mary Anna Venneri Pankaj Trivedi Andrea Lenzi Cinzia Marchese |
author_sort |
Eleni Anastasiadou |
title |
Calcineurin Gamma Catalytic Subunit PPP3CC Inhibition by miR-200c-3p Affects Apoptosis in Epithelial Ovarian Cancer |
title_short |
Calcineurin Gamma Catalytic Subunit PPP3CC Inhibition by miR-200c-3p Affects Apoptosis in Epithelial Ovarian Cancer |
title_full |
Calcineurin Gamma Catalytic Subunit PPP3CC Inhibition by miR-200c-3p Affects Apoptosis in Epithelial Ovarian Cancer |
title_fullStr |
Calcineurin Gamma Catalytic Subunit PPP3CC Inhibition by miR-200c-3p Affects Apoptosis in Epithelial Ovarian Cancer |
title_full_unstemmed |
Calcineurin Gamma Catalytic Subunit PPP3CC Inhibition by miR-200c-3p Affects Apoptosis in Epithelial Ovarian Cancer |
title_sort |
calcineurin gamma catalytic subunit ppp3cc inhibition by mir-200c-3p affects apoptosis in epithelial ovarian cancer |
publisher |
MDPI AG |
series |
Genes |
issn |
2073-4425 |
publishDate |
2021-09-01 |
description |
Epithelial ovarian cancer (EOC) outpaces all the other forms of the female reproductive system malignancies. MicroRNAs have emerged as promising predictive biomarkers to therapeutic treatments as their expression might characterize the tumor stage or grade. In EOC, miR-200c is considered a master regulator of oncogenes or tumor suppressors. To investigate novel miR-200c-3p target genes involved in EOC tumorigenesis, we evaluated the association between this miRNA and the mRNA expression of several potential target genes by RNA-seq data of both 46 EOC cell lines from Cancer Cell line Encyclopedia (CCLE) and 456 EOC patient bio-specimens from The Cancer Genome Atlas (TCGA). Both analyses showed a significant anticorrelation between miR-200c-3p and the protein phosphatase 3 catalytic subunit γ of calcineurin (PPP3CC) levels involved in the apoptosis pathway. Quantitative mRNA expression analysis in patient biopsies confirmed the inverse correlation between miR-200c-3p and PPP3CC levels. In vitro regulation of PPP3CC expression through miR-200c-3p and RNA interference technology led to a concomitant modulation of BCL2- and p-AKT-related pathways, suggesting the tumor suppressive role of PPP3CC in EOC. Our results suggest that inhibition of high expression of miR-200c-3p in EOC might lead to overexpression of the tumor suppressor PPP3CC and subsequent induction of apoptosis in EOC patients. |
topic |
epithelial ovarian cancer miRNA PPP3CC calcineurin apoptosis TCGA and CCLE databases |
url |
https://www.mdpi.com/2073-4425/12/9/1400 |
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