Cargando…

HNRNPL Restrains miR-155 Targeting of BUB1 to Stabilize Aberrant Karyotypes of Transformed Cells in Chronic Lymphocytic Leukemia

Aneuploidy and overexpression of hsa-miR-155-5p (miR-155) characterize most solid and hematological malignancies. We recently demonstrated that miR-155 sustains aneuploidy at early stages of in vitro cellular transformation. During in vitro transformation of normal human fibroblast, upregulation of...

Descripción completa

Detalles Bibliográficos
Autores principales: Pagotto, Sara, Veronese, Angelo, Soranno, Alessandra, Balatti, Veronica, Ramassone, Alice, Guanciali-Franchi, Paolo E., Palka, Giandomenico, Innocenti, Idanna, Autore, Francesco, Rassenti, Laura Z., Kipps, Thomas J., Mariani-Costantini, Renato, Laurenti, Luca, Croce, Carlo M., Visone, Rosa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6520824/
https://www.ncbi.nlm.nih.gov/pubmed/31018621
http://dx.doi.org/10.3390/cancers11040575
_version_ 1783418817868726272
author Pagotto, Sara
Veronese, Angelo
Soranno, Alessandra
Balatti, Veronica
Ramassone, Alice
Guanciali-Franchi, Paolo E.
Palka, Giandomenico
Innocenti, Idanna
Autore, Francesco
Rassenti, Laura Z.
Kipps, Thomas J.
Mariani-Costantini, Renato
Laurenti, Luca
Croce, Carlo M.
Visone, Rosa
author_facet Pagotto, Sara
Veronese, Angelo
Soranno, Alessandra
Balatti, Veronica
Ramassone, Alice
Guanciali-Franchi, Paolo E.
Palka, Giandomenico
Innocenti, Idanna
Autore, Francesco
Rassenti, Laura Z.
Kipps, Thomas J.
Mariani-Costantini, Renato
Laurenti, Luca
Croce, Carlo M.
Visone, Rosa
author_sort Pagotto, Sara
collection PubMed
description Aneuploidy and overexpression of hsa-miR-155-5p (miR-155) characterize most solid and hematological malignancies. We recently demonstrated that miR-155 sustains aneuploidy at early stages of in vitro cellular transformation. During in vitro transformation of normal human fibroblast, upregulation of miR-155 downregulates spindle checkpoint proteins as the mitotic checkpoint serine/threonine kinase budding uninhibited by benzimidazoles 1 (BUB1), the centromere protein F (CENPF) and the zw10 kinetochore protein (ZW10), compromising the chromosome alignment at the metaphase plate and leading to aneuploidy in daughter cells. Here we show that the heterogeneous nuclear ribonucleoprotein L (HNRNPL) binds to the polymorphic marker D2S1888 at the 3′UTR of BUB1 gene, impairs the miR-155 targeting, and restores BUB1 expression in chronic lymphocytic leukemia. This mechanism occurs at advanced passages of cell transformation and allows the expansion of more favorable clones. Our findings have revealed, at least in part, the molecular mechanisms behind the chromosomal stabilization of cell lines and the concept that, to survive, tumor cells cannot continuously change their genetic heritage but need to stabilize the most suitable karyotype.
format Online
Article
Text
id pubmed-6520824
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-65208242019-05-31 HNRNPL Restrains miR-155 Targeting of BUB1 to Stabilize Aberrant Karyotypes of Transformed Cells in Chronic Lymphocytic Leukemia Pagotto, Sara Veronese, Angelo Soranno, Alessandra Balatti, Veronica Ramassone, Alice Guanciali-Franchi, Paolo E. Palka, Giandomenico Innocenti, Idanna Autore, Francesco Rassenti, Laura Z. Kipps, Thomas J. Mariani-Costantini, Renato Laurenti, Luca Croce, Carlo M. Visone, Rosa Cancers (Basel) Article Aneuploidy and overexpression of hsa-miR-155-5p (miR-155) characterize most solid and hematological malignancies. We recently demonstrated that miR-155 sustains aneuploidy at early stages of in vitro cellular transformation. During in vitro transformation of normal human fibroblast, upregulation of miR-155 downregulates spindle checkpoint proteins as the mitotic checkpoint serine/threonine kinase budding uninhibited by benzimidazoles 1 (BUB1), the centromere protein F (CENPF) and the zw10 kinetochore protein (ZW10), compromising the chromosome alignment at the metaphase plate and leading to aneuploidy in daughter cells. Here we show that the heterogeneous nuclear ribonucleoprotein L (HNRNPL) binds to the polymorphic marker D2S1888 at the 3′UTR of BUB1 gene, impairs the miR-155 targeting, and restores BUB1 expression in chronic lymphocytic leukemia. This mechanism occurs at advanced passages of cell transformation and allows the expansion of more favorable clones. Our findings have revealed, at least in part, the molecular mechanisms behind the chromosomal stabilization of cell lines and the concept that, to survive, tumor cells cannot continuously change their genetic heritage but need to stabilize the most suitable karyotype. MDPI 2019-04-23 /pmc/articles/PMC6520824/ /pubmed/31018621 http://dx.doi.org/10.3390/cancers11040575 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
Pagotto, Sara
Veronese, Angelo
Soranno, Alessandra
Balatti, Veronica
Ramassone, Alice
Guanciali-Franchi, Paolo E.
Palka, Giandomenico
Innocenti, Idanna
Autore, Francesco
Rassenti, Laura Z.
Kipps, Thomas J.
Mariani-Costantini, Renato
Laurenti, Luca
Croce, Carlo M.
Visone, Rosa
HNRNPL Restrains miR-155 Targeting of BUB1 to Stabilize Aberrant Karyotypes of Transformed Cells in Chronic Lymphocytic Leukemia
title HNRNPL Restrains miR-155 Targeting of BUB1 to Stabilize Aberrant Karyotypes of Transformed Cells in Chronic Lymphocytic Leukemia
title_full HNRNPL Restrains miR-155 Targeting of BUB1 to Stabilize Aberrant Karyotypes of Transformed Cells in Chronic Lymphocytic Leukemia
title_fullStr HNRNPL Restrains miR-155 Targeting of BUB1 to Stabilize Aberrant Karyotypes of Transformed Cells in Chronic Lymphocytic Leukemia
title_full_unstemmed HNRNPL Restrains miR-155 Targeting of BUB1 to Stabilize Aberrant Karyotypes of Transformed Cells in Chronic Lymphocytic Leukemia
title_short HNRNPL Restrains miR-155 Targeting of BUB1 to Stabilize Aberrant Karyotypes of Transformed Cells in Chronic Lymphocytic Leukemia
title_sort hnrnpl restrains mir-155 targeting of bub1 to stabilize aberrant karyotypes of transformed cells in chronic lymphocytic leukemia
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6520824/
https://www.ncbi.nlm.nih.gov/pubmed/31018621
http://dx.doi.org/10.3390/cancers11040575
work_keys_str_mv AT pagottosara hnrnplrestrainsmir155targetingofbub1tostabilizeaberrantkaryotypesoftransformedcellsinchroniclymphocyticleukemia
AT veroneseangelo hnrnplrestrainsmir155targetingofbub1tostabilizeaberrantkaryotypesoftransformedcellsinchroniclymphocyticleukemia
AT sorannoalessandra hnrnplrestrainsmir155targetingofbub1tostabilizeaberrantkaryotypesoftransformedcellsinchroniclymphocyticleukemia
AT balattiveronica hnrnplrestrainsmir155targetingofbub1tostabilizeaberrantkaryotypesoftransformedcellsinchroniclymphocyticleukemia
AT ramassonealice hnrnplrestrainsmir155targetingofbub1tostabilizeaberrantkaryotypesoftransformedcellsinchroniclymphocyticleukemia
AT guancialifranchipaoloe hnrnplrestrainsmir155targetingofbub1tostabilizeaberrantkaryotypesoftransformedcellsinchroniclymphocyticleukemia
AT palkagiandomenico hnrnplrestrainsmir155targetingofbub1tostabilizeaberrantkaryotypesoftransformedcellsinchroniclymphocyticleukemia
AT innocentiidanna hnrnplrestrainsmir155targetingofbub1tostabilizeaberrantkaryotypesoftransformedcellsinchroniclymphocyticleukemia
AT autorefrancesco hnrnplrestrainsmir155targetingofbub1tostabilizeaberrantkaryotypesoftransformedcellsinchroniclymphocyticleukemia
AT rassentilauraz hnrnplrestrainsmir155targetingofbub1tostabilizeaberrantkaryotypesoftransformedcellsinchroniclymphocyticleukemia
AT kippsthomasj hnrnplrestrainsmir155targetingofbub1tostabilizeaberrantkaryotypesoftransformedcellsinchroniclymphocyticleukemia
AT marianicostantinirenato hnrnplrestrainsmir155targetingofbub1tostabilizeaberrantkaryotypesoftransformedcellsinchroniclymphocyticleukemia
AT laurentiluca hnrnplrestrainsmir155targetingofbub1tostabilizeaberrantkaryotypesoftransformedcellsinchroniclymphocyticleukemia
AT crocecarlom hnrnplrestrainsmir155targetingofbub1tostabilizeaberrantkaryotypesoftransformedcellsinchroniclymphocyticleukemia
AT visonerosa hnrnplrestrainsmir155targetingofbub1tostabilizeaberrantkaryotypesoftransformedcellsinchroniclymphocyticleukemia