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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| Veröffentlicht in: | Genes 2021-09, Vol.12 (9), p.1400 |
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| creator | Anastasiadou, Eleni Messina, Elena Sanavia, Tiziana Labruna, Vittorio Ceccarelli, Simona Megiorni, Francesca Gerini, Giulia Pontecorvi, Paola Camero, Simona Perniola, Giorgia Venneri, Mary Anna Trivedi, Pankaj Lenzi, Andrea Marchese, Cinzia |
| 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. |
| doi_str_mv | 10.3390/genes12091400 |
| format | Article |
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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.</description><identifier>ISSN: 2073-4425</identifier><identifier>EISSN: 2073-4425</identifier><identifier>DOI: 10.3390/genes12091400</identifier><identifier>PMID: 34573382</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>AKT protein ; Apoptosis ; Apoptosis - genetics ; Biomarkers ; Biopsy ; Calcineurin ; Calcineurin - genetics ; Cancer therapies ; Carcinoma, Ovarian Epithelial - genetics ; Carcinoma, Ovarian Epithelial - pathology ; Case-Control Studies ; Cell cycle ; Cell Movement - genetics ; Cell Proliferation - genetics ; Chemotherapy ; Chromosome 3 ; Female ; Gene expression ; Gene Expression Regulation, Enzymologic ; Gene Expression Regulation, Neoplastic ; Genomes ; Humans ; Lymphatic system ; Medical prognosis ; Metastasis ; MicroRNAs ; MicroRNAs - physiology ; miRNA ; Mutation ; Ovarian cancer ; Ovarian Neoplasms - genetics ; Ovarian Neoplasms - pathology ; Phosphatase ; Protein phosphatase ; Reproductive system ; RNA Interference - physiology ; RNA-mediated interference ; Tumor cell lines ; Tumor Cells, Cultured ; Tumor suppressor genes ; Tumorigenesis ; Tumors</subject><ispartof>Genes, 2021-09, Vol.12 (9), p.1400</ispartof><rights>2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2021 by the authors. 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c481t-c3996d1a05e9d433bf73cf66db5875cb0ea15076e367990be57807660b7d0de03</citedby><cites>FETCH-LOGICAL-c481t-c3996d1a05e9d433bf73cf66db5875cb0ea15076e367990be57807660b7d0de03</cites><orcidid>0000-0001-8789-7719 ; 0000-0003-3288-0631 ; 0000-0003-2392-3775 ; 0000-0001-8286-3640 ; 0000-0003-3705-3248 ; 0000-0002-0687-8135 ; 0000-0002-7182-2883 ; 0000-0002-9280-8917 ; 0000-0003-0212-6734 ; 0000-0001-9574-6304</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8470066/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8470066/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34573382$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Anastasiadou, Eleni</creatorcontrib><creatorcontrib>Messina, Elena</creatorcontrib><creatorcontrib>Sanavia, Tiziana</creatorcontrib><creatorcontrib>Labruna, Vittorio</creatorcontrib><creatorcontrib>Ceccarelli, Simona</creatorcontrib><creatorcontrib>Megiorni, Francesca</creatorcontrib><creatorcontrib>Gerini, Giulia</creatorcontrib><creatorcontrib>Pontecorvi, Paola</creatorcontrib><creatorcontrib>Camero, Simona</creatorcontrib><creatorcontrib>Perniola, Giorgia</creatorcontrib><creatorcontrib>Venneri, Mary Anna</creatorcontrib><creatorcontrib>Trivedi, Pankaj</creatorcontrib><creatorcontrib>Lenzi, Andrea</creatorcontrib><creatorcontrib>Marchese, Cinzia</creatorcontrib><title>Calcineurin Gamma Catalytic Subunit PPP3CC Inhibition by miR-200c-3p Affects Apoptosis in Epithelial Ovarian Cancer</title><title>Genes</title><addtitle>Genes (Basel)</addtitle><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.</description><subject>AKT protein</subject><subject>Apoptosis</subject><subject>Apoptosis - genetics</subject><subject>Biomarkers</subject><subject>Biopsy</subject><subject>Calcineurin</subject><subject>Calcineurin - genetics</subject><subject>Cancer therapies</subject><subject>Carcinoma, Ovarian Epithelial - genetics</subject><subject>Carcinoma, Ovarian Epithelial - pathology</subject><subject>Case-Control Studies</subject><subject>Cell cycle</subject><subject>Cell Movement - genetics</subject><subject>Cell Proliferation - genetics</subject><subject>Chemotherapy</subject><subject>Chromosome 3</subject><subject>Female</subject><subject>Gene expression</subject><subject>Gene Expression Regulation, Enzymologic</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Genomes</subject><subject>Humans</subject><subject>Lymphatic system</subject><subject>Medical prognosis</subject><subject>Metastasis</subject><subject>MicroRNAs</subject><subject>MicroRNAs - 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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. 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| ispartof | Genes, 2021-09, Vol.12 (9), p.1400 |
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| subjects | AKT protein Apoptosis Apoptosis - genetics Biomarkers Biopsy Calcineurin Calcineurin - genetics Cancer therapies Carcinoma, Ovarian Epithelial - genetics Carcinoma, Ovarian Epithelial - pathology Case-Control Studies Cell cycle Cell Movement - genetics Cell Proliferation - genetics Chemotherapy Chromosome 3 Female Gene expression Gene Expression Regulation, Enzymologic Gene Expression Regulation, Neoplastic Genomes Humans Lymphatic system Medical prognosis Metastasis MicroRNAs MicroRNAs - physiology miRNA Mutation Ovarian cancer Ovarian Neoplasms - genetics Ovarian Neoplasms - pathology Phosphatase Protein phosphatase Reproductive system RNA Interference - physiology RNA-mediated interference Tumor cell lines Tumor Cells, Cultured Tumor suppressor genes Tumorigenesis Tumors |
| title | Calcineurin Gamma Catalytic Subunit PPP3CC Inhibition by miR-200c-3p Affects Apoptosis in Epithelial Ovarian Cancer |
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