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The Metallophosphoesterase-Domain-Containing Protein 2 (MPPED2) Gene Acts as Tumor Suppressor in Breast Cancer
Background: We have recently reported the downregulation of the Metallophosphoesterase-domain-containing protein 2 (MPPED2) gene and its cognate long non-coding RNA, MPPED2-AS1, in papillary thyroid carcinomas. Functional studies supported a tumor suppressor role of both these genes in thyroid carci...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6627064/ https://www.ncbi.nlm.nih.gov/pubmed/31181813 http://dx.doi.org/10.3390/cancers11060797 |
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author | Pellecchia, Simona Sepe, Romina Federico, Antonella Cuomo, Mariella Credendino, Sara Carmela Pisapia, Pasquale Bellevicine, Claudio Nicolau-Neto, Pedro Severo Ramundo, Mariana Crescenzi, Elvira De Vita, Gabriella Terracciano, Luigi Maria Chiariotti, Lorenzo Fusco, Alfredo Pallante, Pierlorenzo |
author_facet | Pellecchia, Simona Sepe, Romina Federico, Antonella Cuomo, Mariella Credendino, Sara Carmela Pisapia, Pasquale Bellevicine, Claudio Nicolau-Neto, Pedro Severo Ramundo, Mariana Crescenzi, Elvira De Vita, Gabriella Terracciano, Luigi Maria Chiariotti, Lorenzo Fusco, Alfredo Pallante, Pierlorenzo |
author_sort | Pellecchia, Simona |
collection | PubMed |
description | Background: We have recently reported the downregulation of the Metallophosphoesterase-domain-containing protein 2 (MPPED2) gene and its cognate long non-coding RNA, MPPED2-AS1, in papillary thyroid carcinomas. Functional studies supported a tumor suppressor role of both these genes in thyroid carcinogenesis. We then decided to investigate their role in breast carcinogenesis. Methods: In order to verify MPPED2 expression, 45 human breast carcinoma samples have been investigated by quantitative real-time polymerase chain reaction (qRT-PCR). Then, MPPED2 has been transfected in several human breast carcinoma cell lines, analyzing its role in cell proliferation, migration and invasion. To study the regulation of MPPED2 expression the methylation of its promoter was investigated by targeted bisulfite sequencing. Results: MPPED2 expression was decreased in breast cancer samples, and this was confirmed by the analysis of data available in The Cancer Genome Atlas (TCGA). Interestingly, the hypermethylation of MPPED2 promoter likely accounted for its downregulation in breast cancer. Additionally, MPPED2-AS1 was also found downregulated in breast cancer tissues and, intriguingly, its expression decreased the hypermethylation of the MPPED2 promoter by inhibiting DNA methyltransferase 1 (DNMT1). Furthermore, the restoration of MPPED2 expression reduced cell proliferation, migration and invasion capability of breast carcinoma cell lines. Conclusion: Taken together, these results propose MPPED2 downregulation as a critical event in breast carcinogenesis. |
format | Online Article Text |
id | pubmed-6627064 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-66270642019-07-19 The Metallophosphoesterase-Domain-Containing Protein 2 (MPPED2) Gene Acts as Tumor Suppressor in Breast Cancer Pellecchia, Simona Sepe, Romina Federico, Antonella Cuomo, Mariella Credendino, Sara Carmela Pisapia, Pasquale Bellevicine, Claudio Nicolau-Neto, Pedro Severo Ramundo, Mariana Crescenzi, Elvira De Vita, Gabriella Terracciano, Luigi Maria Chiariotti, Lorenzo Fusco, Alfredo Pallante, Pierlorenzo Cancers (Basel) Article Background: We have recently reported the downregulation of the Metallophosphoesterase-domain-containing protein 2 (MPPED2) gene and its cognate long non-coding RNA, MPPED2-AS1, in papillary thyroid carcinomas. Functional studies supported a tumor suppressor role of both these genes in thyroid carcinogenesis. We then decided to investigate their role in breast carcinogenesis. Methods: In order to verify MPPED2 expression, 45 human breast carcinoma samples have been investigated by quantitative real-time polymerase chain reaction (qRT-PCR). Then, MPPED2 has been transfected in several human breast carcinoma cell lines, analyzing its role in cell proliferation, migration and invasion. To study the regulation of MPPED2 expression the methylation of its promoter was investigated by targeted bisulfite sequencing. Results: MPPED2 expression was decreased in breast cancer samples, and this was confirmed by the analysis of data available in The Cancer Genome Atlas (TCGA). Interestingly, the hypermethylation of MPPED2 promoter likely accounted for its downregulation in breast cancer. Additionally, MPPED2-AS1 was also found downregulated in breast cancer tissues and, intriguingly, its expression decreased the hypermethylation of the MPPED2 promoter by inhibiting DNA methyltransferase 1 (DNMT1). Furthermore, the restoration of MPPED2 expression reduced cell proliferation, migration and invasion capability of breast carcinoma cell lines. Conclusion: Taken together, these results propose MPPED2 downregulation as a critical event in breast carcinogenesis. MDPI 2019-06-08 /pmc/articles/PMC6627064/ /pubmed/31181813 http://dx.doi.org/10.3390/cancers11060797 Text en © 2019 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 (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Pellecchia, Simona Sepe, Romina Federico, Antonella Cuomo, Mariella Credendino, Sara Carmela Pisapia, Pasquale Bellevicine, Claudio Nicolau-Neto, Pedro Severo Ramundo, Mariana Crescenzi, Elvira De Vita, Gabriella Terracciano, Luigi Maria Chiariotti, Lorenzo Fusco, Alfredo Pallante, Pierlorenzo The Metallophosphoesterase-Domain-Containing Protein 2 (MPPED2) Gene Acts as Tumor Suppressor in Breast Cancer |
title | The Metallophosphoesterase-Domain-Containing Protein 2 (MPPED2) Gene Acts as Tumor Suppressor in Breast Cancer |
title_full | The Metallophosphoesterase-Domain-Containing Protein 2 (MPPED2) Gene Acts as Tumor Suppressor in Breast Cancer |
title_fullStr | The Metallophosphoesterase-Domain-Containing Protein 2 (MPPED2) Gene Acts as Tumor Suppressor in Breast Cancer |
title_full_unstemmed | The Metallophosphoesterase-Domain-Containing Protein 2 (MPPED2) Gene Acts as Tumor Suppressor in Breast Cancer |
title_short | The Metallophosphoesterase-Domain-Containing Protein 2 (MPPED2) Gene Acts as Tumor Suppressor in Breast Cancer |
title_sort | metallophosphoesterase-domain-containing protein 2 (mpped2) gene acts as tumor suppressor in breast cancer |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6627064/ https://www.ncbi.nlm.nih.gov/pubmed/31181813 http://dx.doi.org/10.3390/cancers11060797 |
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