Cargando…
Intermittent Hypoxia Mediates Paraspeckle Protein-1 Upregulation in Sleep Apnea
SIMPLE SUMMARY: Patients with obstructive sleep apnea (OSA) exhibit an intermittent hypoxia-dependent paraspeckle protein-1 (PSPC1) increase, which is eventually delivered to the plasma through its cleavage from OSA monocytes by matrix metalloprotease-2, promoting tumor growth factor (TGFβ) expressi...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8345391/ https://www.ncbi.nlm.nih.gov/pubmed/34359789 http://dx.doi.org/10.3390/cancers13153888 |
_version_ | 1783734616069242880 |
---|---|
author | Díaz-García, Elena García-Tovar, Sara Casitas, Raquel Jaureguizar, Ana Zamarrón, Ester Sánchez-Sánchez, Begoña Sastre-Perona, Ana López-Collazo, Eduardo Garcia-Rio, Francisco Cubillos-Zapata, Carolina |
author_facet | Díaz-García, Elena García-Tovar, Sara Casitas, Raquel Jaureguizar, Ana Zamarrón, Ester Sánchez-Sánchez, Begoña Sastre-Perona, Ana López-Collazo, Eduardo Garcia-Rio, Francisco Cubillos-Zapata, Carolina |
author_sort | Díaz-García, Elena |
collection | PubMed |
description | SIMPLE SUMMARY: Patients with obstructive sleep apnea (OSA) exhibit an intermittent hypoxia-dependent paraspeckle protein-1 (PSPC1) increase, which is eventually delivered to the plasma through its cleavage from OSA monocytes by matrix metalloprotease-2, promoting tumor growth factor (TGFβ) expression and increasing epithelial-to-mesenchymal transition in a tumor functional model using a melanoma cell line. These results connect the phenomena of sleep apnea with increased plasma PSPC1 levels, which has a functional effect on the TGFβ pathway and accelerates tumor progression. ABSTRACT: As some evidence suggests that hypoxia might be an inducer of nuclear paraspeckle formation, we explore whether intermittent hypoxia (IH)-mediated paraspeckle protein-1 (PSPC1) overexpression might contribute to the activation of tumor growth factor (TGF)β-SMAD pathway in patients with obstructive sleep apnea (OSA). This activation would promote changes in intracellular signaling that would explain the increased cancer aggressiveness reported in these patients. Here, we show that patients with OSA exhibit elevated PSPC1 levels both in plasma and in monocytes. Our data suggest that PSPC1 is ultimately delivered to the plasma through its cleavage from OSA monocytes by matrix metalloproteinase-2 (MMP2). In addition, IH promotes PSPC1, TGFβ, and MMP2 expression in monocytes through the hypoxia-inducible factor. Lastly, both PSPC1 and TGFβ induce increased expression of genes that drive the epithelial-to-mesenchymal transition. Our study details the mechanism by which hypoxemia upmodulates the extracellular release of PSPC1 by means of MMP2, such that plasma PSPC1 together with TGFβ activation signaling further promotes tumor metastasis and supports cancer aggressiveness in patients with OSA. |
format | Online Article Text |
id | pubmed-8345391 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-83453912021-08-07 Intermittent Hypoxia Mediates Paraspeckle Protein-1 Upregulation in Sleep Apnea Díaz-García, Elena García-Tovar, Sara Casitas, Raquel Jaureguizar, Ana Zamarrón, Ester Sánchez-Sánchez, Begoña Sastre-Perona, Ana López-Collazo, Eduardo Garcia-Rio, Francisco Cubillos-Zapata, Carolina Cancers (Basel) Article SIMPLE SUMMARY: Patients with obstructive sleep apnea (OSA) exhibit an intermittent hypoxia-dependent paraspeckle protein-1 (PSPC1) increase, which is eventually delivered to the plasma through its cleavage from OSA monocytes by matrix metalloprotease-2, promoting tumor growth factor (TGFβ) expression and increasing epithelial-to-mesenchymal transition in a tumor functional model using a melanoma cell line. These results connect the phenomena of sleep apnea with increased plasma PSPC1 levels, which has a functional effect on the TGFβ pathway and accelerates tumor progression. ABSTRACT: As some evidence suggests that hypoxia might be an inducer of nuclear paraspeckle formation, we explore whether intermittent hypoxia (IH)-mediated paraspeckle protein-1 (PSPC1) overexpression might contribute to the activation of tumor growth factor (TGF)β-SMAD pathway in patients with obstructive sleep apnea (OSA). This activation would promote changes in intracellular signaling that would explain the increased cancer aggressiveness reported in these patients. Here, we show that patients with OSA exhibit elevated PSPC1 levels both in plasma and in monocytes. Our data suggest that PSPC1 is ultimately delivered to the plasma through its cleavage from OSA monocytes by matrix metalloproteinase-2 (MMP2). In addition, IH promotes PSPC1, TGFβ, and MMP2 expression in monocytes through the hypoxia-inducible factor. Lastly, both PSPC1 and TGFβ induce increased expression of genes that drive the epithelial-to-mesenchymal transition. Our study details the mechanism by which hypoxemia upmodulates the extracellular release of PSPC1 by means of MMP2, such that plasma PSPC1 together with TGFβ activation signaling further promotes tumor metastasis and supports cancer aggressiveness in patients with OSA. MDPI 2021-08-02 /pmc/articles/PMC8345391/ /pubmed/34359789 http://dx.doi.org/10.3390/cancers13153888 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 Díaz-García, Elena García-Tovar, Sara Casitas, Raquel Jaureguizar, Ana Zamarrón, Ester Sánchez-Sánchez, Begoña Sastre-Perona, Ana López-Collazo, Eduardo Garcia-Rio, Francisco Cubillos-Zapata, Carolina Intermittent Hypoxia Mediates Paraspeckle Protein-1 Upregulation in Sleep Apnea |
title | Intermittent Hypoxia Mediates Paraspeckle Protein-1 Upregulation in Sleep Apnea |
title_full | Intermittent Hypoxia Mediates Paraspeckle Protein-1 Upregulation in Sleep Apnea |
title_fullStr | Intermittent Hypoxia Mediates Paraspeckle Protein-1 Upregulation in Sleep Apnea |
title_full_unstemmed | Intermittent Hypoxia Mediates Paraspeckle Protein-1 Upregulation in Sleep Apnea |
title_short | Intermittent Hypoxia Mediates Paraspeckle Protein-1 Upregulation in Sleep Apnea |
title_sort | intermittent hypoxia mediates paraspeckle protein-1 upregulation in sleep apnea |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8345391/ https://www.ncbi.nlm.nih.gov/pubmed/34359789 http://dx.doi.org/10.3390/cancers13153888 |
work_keys_str_mv | AT diazgarciaelena intermittenthypoxiamediatesparaspeckleprotein1upregulationinsleepapnea AT garciatovarsara intermittenthypoxiamediatesparaspeckleprotein1upregulationinsleepapnea AT casitasraquel intermittenthypoxiamediatesparaspeckleprotein1upregulationinsleepapnea AT jaureguizarana intermittenthypoxiamediatesparaspeckleprotein1upregulationinsleepapnea AT zamarronester intermittenthypoxiamediatesparaspeckleprotein1upregulationinsleepapnea AT sanchezsanchezbegona intermittenthypoxiamediatesparaspeckleprotein1upregulationinsleepapnea AT sastreperonaana intermittenthypoxiamediatesparaspeckleprotein1upregulationinsleepapnea AT lopezcollazoeduardo intermittenthypoxiamediatesparaspeckleprotein1upregulationinsleepapnea AT garciariofrancisco intermittenthypoxiamediatesparaspeckleprotein1upregulationinsleepapnea AT cubilloszapatacarolina intermittenthypoxiamediatesparaspeckleprotein1upregulationinsleepapnea |