Expression of immunoproteasome genes is regulated by cell-intrinsic and –extrinsic factors in human cancers

Based on transcriptomic analyses of thousands of samples from The Cancer Genome Atlas, we report that expression of constitutive proteasome (CP) genes (PSMB5, PSMB6, PSMB7) and immunoproteasome (IP) genes (PSMB8, PSMB9, PSMB10) is increased in most cancer types. In breast cancer, expression of IP ge...

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Main Authors:	Rouette, Alexandre, Trofimov, Assya, Haberl, David, Boucher, Geneviève, Lavallée, Vincent-Philippe, D’Angelo, Giovanni, Hébert, Josée, Sauvageau, Guy, Lemieux, Sébastien, Perreault, Claude
Format:	Online
Language:	English
Published:	Nature Publishing Group 2016
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5034284/

id	pubmed-5034284
recordtype	oai_dc
spelling	pubmed-50342842016-09-29 Expression of immunoproteasome genes is regulated by cell-intrinsic and –extrinsic factors in human cancers Rouette, Alexandre Trofimov, Assya Haberl, David Boucher, Geneviève Lavallée, Vincent-Philippe D’Angelo, Giovanni Hébert, Josée Sauvageau, Guy Lemieux, Sébastien Perreault, Claude Article Based on transcriptomic analyses of thousands of samples from The Cancer Genome Atlas, we report that expression of constitutive proteasome (CP) genes (PSMB5, PSMB6, PSMB7) and immunoproteasome (IP) genes (PSMB8, PSMB9, PSMB10) is increased in most cancer types. In breast cancer, expression of IP genes was determined by the abundance of tumor infiltrating lymphocytes and high expression of IP genes was associated with longer survival. In contrast, IP upregulation in acute myeloid leukemia (AML) was a cell-intrinsic feature that was not associated with longer survival. Expression of IP genes in AML was IFN-independent, correlated with the methylation status of IP genes, and was particularly high in AML with an M5 phenotype and/or MLL rearrangement. Notably, PSMB8 inhibition led to accumulation of polyubiquitinated proteins and cell death in IPhigh but not IPlow AML cells. Co-clustering analysis revealed that genes correlated with IP subunits in non-M5 AMLs were primarily implicated in immune processes. However, in M5 AML, IP genes were primarily co-regulated with genes involved in cell metabolism and proliferation, mitochondrial activity and stress responses. We conclude that M5 AML cells can upregulate IP genes in a cell-intrinsic manner in order to resist cell stress. Nature Publishing Group 2016-09-23 /pmc/articles/PMC5034284/ /pubmed/27659694 http://dx.doi.org/10.1038/srep34019 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Rouette, Alexandre Trofimov, Assya Haberl, David Boucher, Geneviève Lavallée, Vincent-Philippe D’Angelo, Giovanni Hébert, Josée Sauvageau, Guy Lemieux, Sébastien Perreault, Claude
spellingShingle	Rouette, Alexandre Trofimov, Assya Haberl, David Boucher, Geneviève Lavallée, Vincent-Philippe D’Angelo, Giovanni Hébert, Josée Sauvageau, Guy Lemieux, Sébastien Perreault, Claude Expression of immunoproteasome genes is regulated by cell-intrinsic and –extrinsic factors in human cancers
author_facet	Rouette, Alexandre Trofimov, Assya Haberl, David Boucher, Geneviève Lavallée, Vincent-Philippe D’Angelo, Giovanni Hébert, Josée Sauvageau, Guy Lemieux, Sébastien Perreault, Claude
author_sort	Rouette, Alexandre
title	Expression of immunoproteasome genes is regulated by cell-intrinsic and –extrinsic factors in human cancers
title_short	Expression of immunoproteasome genes is regulated by cell-intrinsic and –extrinsic factors in human cancers
title_full	Expression of immunoproteasome genes is regulated by cell-intrinsic and –extrinsic factors in human cancers
title_fullStr	Expression of immunoproteasome genes is regulated by cell-intrinsic and –extrinsic factors in human cancers
title_full_unstemmed	Expression of immunoproteasome genes is regulated by cell-intrinsic and –extrinsic factors in human cancers
title_sort	expression of immunoproteasome genes is regulated by cell-intrinsic and –extrinsic factors in human cancers
description	Based on transcriptomic analyses of thousands of samples from The Cancer Genome Atlas, we report that expression of constitutive proteasome (CP) genes (PSMB5, PSMB6, PSMB7) and immunoproteasome (IP) genes (PSMB8, PSMB9, PSMB10) is increased in most cancer types. In breast cancer, expression of IP genes was determined by the abundance of tumor infiltrating lymphocytes and high expression of IP genes was associated with longer survival. In contrast, IP upregulation in acute myeloid leukemia (AML) was a cell-intrinsic feature that was not associated with longer survival. Expression of IP genes in AML was IFN-independent, correlated with the methylation status of IP genes, and was particularly high in AML with an M5 phenotype and/or MLL rearrangement. Notably, PSMB8 inhibition led to accumulation of polyubiquitinated proteins and cell death in IPhigh but not IPlow AML cells. Co-clustering analysis revealed that genes correlated with IP subunits in non-M5 AMLs were primarily implicated in immune processes. However, in M5 AML, IP genes were primarily co-regulated with genes involved in cell metabolism and proliferation, mitochondrial activity and stress responses. We conclude that M5 AML cells can upregulate IP genes in a cell-intrinsic manner in order to resist cell stress.
publisher	Nature Publishing Group
publishDate	2016
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5034284/
_version_	1613659311395831808

Expression of immunoproteasome genes is regulated by cell-intrinsic and –extrinsic factors in human cancers

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