The Metallophosphoesterase-Domain-Containing Protein 2 (MPPED2) Gene Acts as Tumor Suppressor in Breast Cancer

Autor: Lorenzo Chiariotti, Simona Pellecchia, Romina Sepe, Mariana Severo Ramundo, Elvira Crescenzi, Pasquale Pisapia, Pierlorenzo Pallante, Gabriella De Vita, Claudio Bellevicine, Mariella Cuomo, Luigi Terracciano, Alfredo Fusco, Antonella Federico, Sara Carmela Credendino, Pedro Nicolau-Neto
Přispěvatelé: 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
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: Cancers, Vol 11, Iss 6, p 797 (2019)
Cancers (Basel) 11 (2019). doi:10.3390/cancers11060797
info:cnr-pdr/source/autori:Pellecchia S.; Sepe R.; Federico A.; Cuomo M.; Credendino S.C.; Pisapia P.; Bellevicine C.; Nicolau-Neto P.; Ramundo M.S.; Crescenzi E.; de Vita G.; Terracciano L.M.; Chiariotti L.; Fusco A.; Pallante P./titolo:The metallophosphoesterase-domain-containing protein 2 (MPPED2) gene acts as tumor suppressor in breast cancer/doi:10.3390%2Fcancers11060797/rivista:Cancers (Basel)/anno:2019/pagina_da:/pagina_a:/intervallo_pagine:/volume:11
Cancers
Volume 11
Issue 6
ISSN: 2072-6694
DOI: 10.3390/cancers11060797
Popis: 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.
Databáze: OpenAIRE
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