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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...
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/PMC6520824/ https://www.ncbi.nlm.nih.gov/pubmed/31018621 http://dx.doi.org/10.3390/cancers11040575 |
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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 |
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