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Transcriptomic Changes Following Partial Depletion of CENP-E in Normal Human Fibroblasts

The centromere is a fundamental chromosome structure in which the macro-molecular kinetochore assembles and is bound by spindle microtubules, allowing the segregation of sister chromatids during mitosis. Any alterations in kinetochore assembly or functioning or kinetochore–microtubule attachments je...

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Autores principales: Cilluffo, Danilo, Chiavetta, Roberta Flavia, Bivona, Serena, Contino, Flavia, Coronnello, Claudia, Feo, Salvatore, Di Leonardo, Aldo, Barra, Viviana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8466516/
https://www.ncbi.nlm.nih.gov/pubmed/34573304
http://dx.doi.org/10.3390/genes12091322
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author Cilluffo, Danilo
Chiavetta, Roberta Flavia
Bivona, Serena
Contino, Flavia
Coronnello, Claudia
Feo, Salvatore
Di Leonardo, Aldo
Barra, Viviana
author_facet Cilluffo, Danilo
Chiavetta, Roberta Flavia
Bivona, Serena
Contino, Flavia
Coronnello, Claudia
Feo, Salvatore
Di Leonardo, Aldo
Barra, Viviana
author_sort Cilluffo, Danilo
collection PubMed
description The centromere is a fundamental chromosome structure in which the macro-molecular kinetochore assembles and is bound by spindle microtubules, allowing the segregation of sister chromatids during mitosis. Any alterations in kinetochore assembly or functioning or kinetochore–microtubule attachments jeopardize chromosome stability, leading to aneuploidy, a common feature of cancer cells. The spindle assembly checkpoint (SAC) supervises this process, ensuring a faithful segregation of chromosomes. CENP-E is both a protein of the kinetochore and a crucial component of the SAC required for kinetochore–microtubule capture and stable attachment, as well as congression of chromosomes to the metaphase plate. As the function of CENP-E is restricted to mitosis, its haploinsufficiency has been used to study the induced cell aneuploidy; however, the gene expression profile triggered by CENP-E reduction in normal cells has never been explored. To fill this gap, here we investigated whether a gene network exists that is associated with an siRNA-induced 50% reduction in CENP-E and consequent aneuploidy. Gene expression microarray analyses were performed at early and late timepoints after transfection. Initially, cell cycle regulation and stress response pathways were downregulated, while afterwards pathways involved in epithelial–mesenchymal transition, hypoxia and xenobiotic metabolism were altered. Collectively, our results suggest that CENP-E reduction triggers a gene expression program that recapitulates some features of tumor cells.
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spelling pubmed-84665162021-09-27 Transcriptomic Changes Following Partial Depletion of CENP-E in Normal Human Fibroblasts Cilluffo, Danilo Chiavetta, Roberta Flavia Bivona, Serena Contino, Flavia Coronnello, Claudia Feo, Salvatore Di Leonardo, Aldo Barra, Viviana Genes (Basel) Article The centromere is a fundamental chromosome structure in which the macro-molecular kinetochore assembles and is bound by spindle microtubules, allowing the segregation of sister chromatids during mitosis. Any alterations in kinetochore assembly or functioning or kinetochore–microtubule attachments jeopardize chromosome stability, leading to aneuploidy, a common feature of cancer cells. The spindle assembly checkpoint (SAC) supervises this process, ensuring a faithful segregation of chromosomes. CENP-E is both a protein of the kinetochore and a crucial component of the SAC required for kinetochore–microtubule capture and stable attachment, as well as congression of chromosomes to the metaphase plate. As the function of CENP-E is restricted to mitosis, its haploinsufficiency has been used to study the induced cell aneuploidy; however, the gene expression profile triggered by CENP-E reduction in normal cells has never been explored. To fill this gap, here we investigated whether a gene network exists that is associated with an siRNA-induced 50% reduction in CENP-E and consequent aneuploidy. Gene expression microarray analyses were performed at early and late timepoints after transfection. Initially, cell cycle regulation and stress response pathways were downregulated, while afterwards pathways involved in epithelial–mesenchymal transition, hypoxia and xenobiotic metabolism were altered. Collectively, our results suggest that CENP-E reduction triggers a gene expression program that recapitulates some features of tumor cells. MDPI 2021-08-26 /pmc/articles/PMC8466516/ /pubmed/34573304 http://dx.doi.org/10.3390/genes12091322 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Cilluffo, Danilo
Chiavetta, Roberta Flavia
Bivona, Serena
Contino, Flavia
Coronnello, Claudia
Feo, Salvatore
Di Leonardo, Aldo
Barra, Viviana
Transcriptomic Changes Following Partial Depletion of CENP-E in Normal Human Fibroblasts
title Transcriptomic Changes Following Partial Depletion of CENP-E in Normal Human Fibroblasts
title_full Transcriptomic Changes Following Partial Depletion of CENP-E in Normal Human Fibroblasts
title_fullStr Transcriptomic Changes Following Partial Depletion of CENP-E in Normal Human Fibroblasts
title_full_unstemmed Transcriptomic Changes Following Partial Depletion of CENP-E in Normal Human Fibroblasts
title_short Transcriptomic Changes Following Partial Depletion of CENP-E in Normal Human Fibroblasts
title_sort transcriptomic changes following partial depletion of cenp-e in normal human fibroblasts
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8466516/
https://www.ncbi.nlm.nih.gov/pubmed/34573304
http://dx.doi.org/10.3390/genes12091322
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