DNA-demethylating and anti-tumor activity of synthetic miR-29b mimics in multiple myeloma

Aberrant DNA methylation plays a relevant role in multiple myeloma (MM) pathogenesis. MicroRNAs (miRNAs) are a class of small non-coding RNAs that recently emerged as master regulator of gene expression by targeting protein-coding mRNAs. However, miRNAs involvement in the regulation of the epigeneti...

Full description

Bibliographic Details
Main Authors:	Amodio, Nicola, Leotta, Marzia, Bellizzi, Dina, Di Martino, Maria Teresa, D'Aquila, Patrizia, Lionetti, Marta, Fabiani, Fernanda, Leone, Emanuela, Gullà, Anna Maria, Passarino, Giuseppe, Caraglia, Michele, Negrini, Massimo, Neri, Antonino, Giordano, Antonio, Tagliaferri, Pierosandro, Tassone, Pierfrancesco
Format:	Online
Language:	English
Published:	Impact Journals LLC 2012
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3717964/

id	pubmed-3717964
recordtype	oai_dc
spelling	pubmed-37179642013-07-25 DNA-demethylating and anti-tumor activity of synthetic miR-29b mimics in multiple myeloma Amodio, Nicola Leotta, Marzia Bellizzi, Dina Di Martino, Maria Teresa D'Aquila, Patrizia Lionetti, Marta Fabiani, Fernanda Leone, Emanuela Gullà, Anna Maria Passarino, Giuseppe Caraglia, Michele Negrini, Massimo Neri, Antonino Giordano, Antonio Tagliaferri, Pierosandro Tassone, Pierfrancesco Research Papers Aberrant DNA methylation plays a relevant role in multiple myeloma (MM) pathogenesis. MicroRNAs (miRNAs) are a class of small non-coding RNAs that recently emerged as master regulator of gene expression by targeting protein-coding mRNAs. However, miRNAs involvement in the regulation of the epigenetic machinery and their potential use as therapeutics in MM remain to be investigated. Here, we provide evidence that the expression of de novo DNA methyltransferases (DNMTs) is deregulated in MM cells. Moreover, we show that miR-29b targets DNMT3A and DNMT3B mRNAs and reduces global DNA methylation in MM cells. In vitro transfection of MM cells with synthetic miR-29b mimics significantly impairs cell cycle progression and also potentiates the growth-inhibitory effects induced by the demethylating agent 5-azacitidine. Most importantly, in vivo intratumor or systemic delivery of synthetic miR-29b mimics, in two clinically relevant murine models of human MM, including the SCID-synth-hu system, induces significant anti-tumor effects. All together, our findings demonstrate that aberrant DNMTs expression is efficiently modulated by tumor suppressive synthetic miR-29b mimics, indicating that methyloma modulation is a novel matter of investigation in miRNA-based therapy of MM. Impact Journals LLC 2012-10-21 /pmc/articles/PMC3717964/ /pubmed/23100393 Text en Copyright: © 2012 Amodio et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Amodio, Nicola Leotta, Marzia Bellizzi, Dina Di Martino, Maria Teresa D'Aquila, Patrizia Lionetti, Marta Fabiani, Fernanda Leone, Emanuela Gullà, Anna Maria Passarino, Giuseppe Caraglia, Michele Negrini, Massimo Neri, Antonino Giordano, Antonio Tagliaferri, Pierosandro Tassone, Pierfrancesco
spellingShingle	Amodio, Nicola Leotta, Marzia Bellizzi, Dina Di Martino, Maria Teresa D'Aquila, Patrizia Lionetti, Marta Fabiani, Fernanda Leone, Emanuela Gullà, Anna Maria Passarino, Giuseppe Caraglia, Michele Negrini, Massimo Neri, Antonino Giordano, Antonio Tagliaferri, Pierosandro Tassone, Pierfrancesco DNA-demethylating and anti-tumor activity of synthetic miR-29b mimics in multiple myeloma
author_facet	Amodio, Nicola Leotta, Marzia Bellizzi, Dina Di Martino, Maria Teresa D'Aquila, Patrizia Lionetti, Marta Fabiani, Fernanda Leone, Emanuela Gullà, Anna Maria Passarino, Giuseppe Caraglia, Michele Negrini, Massimo Neri, Antonino Giordano, Antonio Tagliaferri, Pierosandro Tassone, Pierfrancesco
author_sort	Amodio, Nicola
title	DNA-demethylating and anti-tumor activity of synthetic miR-29b mimics in multiple myeloma
title_short	DNA-demethylating and anti-tumor activity of synthetic miR-29b mimics in multiple myeloma
title_full	DNA-demethylating and anti-tumor activity of synthetic miR-29b mimics in multiple myeloma
title_fullStr	DNA-demethylating and anti-tumor activity of synthetic miR-29b mimics in multiple myeloma
title_full_unstemmed	DNA-demethylating and anti-tumor activity of synthetic miR-29b mimics in multiple myeloma
title_sort	dna-demethylating and anti-tumor activity of synthetic mir-29b mimics in multiple myeloma
description	Aberrant DNA methylation plays a relevant role in multiple myeloma (MM) pathogenesis. MicroRNAs (miRNAs) are a class of small non-coding RNAs that recently emerged as master regulator of gene expression by targeting protein-coding mRNAs. However, miRNAs involvement in the regulation of the epigenetic machinery and their potential use as therapeutics in MM remain to be investigated. Here, we provide evidence that the expression of de novo DNA methyltransferases (DNMTs) is deregulated in MM cells. Moreover, we show that miR-29b targets DNMT3A and DNMT3B mRNAs and reduces global DNA methylation in MM cells. In vitro transfection of MM cells with synthetic miR-29b mimics significantly impairs cell cycle progression and also potentiates the growth-inhibitory effects induced by the demethylating agent 5-azacitidine. Most importantly, in vivo intratumor or systemic delivery of synthetic miR-29b mimics, in two clinically relevant murine models of human MM, including the SCID-synth-hu system, induces significant anti-tumor effects. All together, our findings demonstrate that aberrant DNMTs expression is efficiently modulated by tumor suppressive synthetic miR-29b mimics, indicating that methyloma modulation is a novel matter of investigation in miRNA-based therapy of MM.
publisher	Impact Journals LLC
publishDate	2012
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3717964/
_version_	1611996660557152256

DNA-demethylating and anti-tumor activity of synthetic miR-29b mimics in multiple myeloma

Similar Items