Cargando…

Expression Pattern and Biological Significance of the lncRNA ST3GAL6-AS1 in Multiple Myeloma

The biological impact of long non-coding RNAs (lncRNAs) in multiple myeloma (MM) is becoming an important aspect of investigation, which may contribute to the understanding of the complex pathobiology of the disease whilst also providing novel potential therapeutic targets. Herein, we investigated t...

Descripción completa

Detalles Bibliográficos
Autores principales: Ronchetti, Domenica, Todoerti, Katia, Vinci, Cristina, Favasuli, Vanessa, Agnelli, Luca, Manzoni, Martina, Pelizzoni, Francesca, Chiaramonte, Raffaella, Platonova, Natalia, Giuliani, Nicola, Tassone, Pierfrancesco, Amodio, Nicola, Neri, Antonino, Taiana, Elisa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7225964/
https://www.ncbi.nlm.nih.gov/pubmed/32218309
http://dx.doi.org/10.3390/cancers12040782
_version_ 1783534176136331264
author Ronchetti, Domenica
Todoerti, Katia
Vinci, Cristina
Favasuli, Vanessa
Agnelli, Luca
Manzoni, Martina
Pelizzoni, Francesca
Chiaramonte, Raffaella
Platonova, Natalia
Giuliani, Nicola
Tassone, Pierfrancesco
Amodio, Nicola
Neri, Antonino
Taiana, Elisa
author_facet Ronchetti, Domenica
Todoerti, Katia
Vinci, Cristina
Favasuli, Vanessa
Agnelli, Luca
Manzoni, Martina
Pelizzoni, Francesca
Chiaramonte, Raffaella
Platonova, Natalia
Giuliani, Nicola
Tassone, Pierfrancesco
Amodio, Nicola
Neri, Antonino
Taiana, Elisa
author_sort Ronchetti, Domenica
collection PubMed
description The biological impact of long non-coding RNAs (lncRNAs) in multiple myeloma (MM) is becoming an important aspect of investigation, which may contribute to the understanding of the complex pathobiology of the disease whilst also providing novel potential therapeutic targets. Herein, we investigated the expression pattern and the biological significance of the lncRNA ST3 beta-galactoside alpha-2,3 sialyltransferase 6 antisense RNA 1 (ST3GAL6-AS1) in MM. We documented a high ST3GAL6-AS1 expression level in MM compared to normal plasma cells (PCs) or other hematological malignancies. Transcriptome analyses of MM PCs from patients included in the CoMMpass database indicated a potential involvement of ST3GAL6-AS1 in MAPK signaling and ubiquitin-mediated proteolysis pathways. ST3GAL6-AS1 silencing by LNA-gapmeR antisense oligonucleotides inhibits cell proliferation and triggers apoptosis in MM cell line. Notably, ST3GAL6-AS1 silencing in vitro displayed the down-regulation of the MAPK pathway and protein ubiquitination. These data suggest that ST3GAL6-AS1 deregulation may play a pathogenetic role in MM by affecting both proliferation pathways and circuits fundamental for PC survival. However, ST3GAL6-AS1 expression levels seem not to be significantly associated with clinical outcome and its targeting appears to exert antagonistic effects with proteasome inhibitors used in MM. These findings strongly urge the need for further studies investigating the relevance of ST3GAL6-AS1 in MM.
format Online
Article
Text
id pubmed-7225964
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-72259642020-05-18 Expression Pattern and Biological Significance of the lncRNA ST3GAL6-AS1 in Multiple Myeloma Ronchetti, Domenica Todoerti, Katia Vinci, Cristina Favasuli, Vanessa Agnelli, Luca Manzoni, Martina Pelizzoni, Francesca Chiaramonte, Raffaella Platonova, Natalia Giuliani, Nicola Tassone, Pierfrancesco Amodio, Nicola Neri, Antonino Taiana, Elisa Cancers (Basel) Article The biological impact of long non-coding RNAs (lncRNAs) in multiple myeloma (MM) is becoming an important aspect of investigation, which may contribute to the understanding of the complex pathobiology of the disease whilst also providing novel potential therapeutic targets. Herein, we investigated the expression pattern and the biological significance of the lncRNA ST3 beta-galactoside alpha-2,3 sialyltransferase 6 antisense RNA 1 (ST3GAL6-AS1) in MM. We documented a high ST3GAL6-AS1 expression level in MM compared to normal plasma cells (PCs) or other hematological malignancies. Transcriptome analyses of MM PCs from patients included in the CoMMpass database indicated a potential involvement of ST3GAL6-AS1 in MAPK signaling and ubiquitin-mediated proteolysis pathways. ST3GAL6-AS1 silencing by LNA-gapmeR antisense oligonucleotides inhibits cell proliferation and triggers apoptosis in MM cell line. Notably, ST3GAL6-AS1 silencing in vitro displayed the down-regulation of the MAPK pathway and protein ubiquitination. These data suggest that ST3GAL6-AS1 deregulation may play a pathogenetic role in MM by affecting both proliferation pathways and circuits fundamental for PC survival. However, ST3GAL6-AS1 expression levels seem not to be significantly associated with clinical outcome and its targeting appears to exert antagonistic effects with proteasome inhibitors used in MM. These findings strongly urge the need for further studies investigating the relevance of ST3GAL6-AS1 in MM. MDPI 2020-03-25 /pmc/articles/PMC7225964/ /pubmed/32218309 http://dx.doi.org/10.3390/cancers12040782 Text en © 2020 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
Ronchetti, Domenica
Todoerti, Katia
Vinci, Cristina
Favasuli, Vanessa
Agnelli, Luca
Manzoni, Martina
Pelizzoni, Francesca
Chiaramonte, Raffaella
Platonova, Natalia
Giuliani, Nicola
Tassone, Pierfrancesco
Amodio, Nicola
Neri, Antonino
Taiana, Elisa
Expression Pattern and Biological Significance of the lncRNA ST3GAL6-AS1 in Multiple Myeloma
title Expression Pattern and Biological Significance of the lncRNA ST3GAL6-AS1 in Multiple Myeloma
title_full Expression Pattern and Biological Significance of the lncRNA ST3GAL6-AS1 in Multiple Myeloma
title_fullStr Expression Pattern and Biological Significance of the lncRNA ST3GAL6-AS1 in Multiple Myeloma
title_full_unstemmed Expression Pattern and Biological Significance of the lncRNA ST3GAL6-AS1 in Multiple Myeloma
title_short Expression Pattern and Biological Significance of the lncRNA ST3GAL6-AS1 in Multiple Myeloma
title_sort expression pattern and biological significance of the lncrna st3gal6-as1 in multiple myeloma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7225964/
https://www.ncbi.nlm.nih.gov/pubmed/32218309
http://dx.doi.org/10.3390/cancers12040782
work_keys_str_mv AT ronchettidomenica expressionpatternandbiologicalsignificanceofthelncrnast3gal6as1inmultiplemyeloma
AT todoertikatia expressionpatternandbiologicalsignificanceofthelncrnast3gal6as1inmultiplemyeloma
AT vincicristina expressionpatternandbiologicalsignificanceofthelncrnast3gal6as1inmultiplemyeloma
AT favasulivanessa expressionpatternandbiologicalsignificanceofthelncrnast3gal6as1inmultiplemyeloma
AT agnelliluca expressionpatternandbiologicalsignificanceofthelncrnast3gal6as1inmultiplemyeloma
AT manzonimartina expressionpatternandbiologicalsignificanceofthelncrnast3gal6as1inmultiplemyeloma
AT pelizzonifrancesca expressionpatternandbiologicalsignificanceofthelncrnast3gal6as1inmultiplemyeloma
AT chiaramonteraffaella expressionpatternandbiologicalsignificanceofthelncrnast3gal6as1inmultiplemyeloma
AT platonovanatalia expressionpatternandbiologicalsignificanceofthelncrnast3gal6as1inmultiplemyeloma
AT giulianinicola expressionpatternandbiologicalsignificanceofthelncrnast3gal6as1inmultiplemyeloma
AT tassonepierfrancesco expressionpatternandbiologicalsignificanceofthelncrnast3gal6as1inmultiplemyeloma
AT amodionicola expressionpatternandbiologicalsignificanceofthelncrnast3gal6as1inmultiplemyeloma
AT neriantonino expressionpatternandbiologicalsignificanceofthelncrnast3gal6as1inmultiplemyeloma
AT taianaelisa expressionpatternandbiologicalsignificanceofthelncrnast3gal6as1inmultiplemyeloma