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Signatures of Co-Deregulated Genes and Their Transcriptional Regulators in Kidney Cancers

There are several studies on the deregulated gene expression profiles in kidney cancer, with varying results depending on the tumor histology and other parameters. None of these, however, have identified the networks that the co-deregulated genes (co-DEGs), across different studies, create. Here, we...

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Autores principales: Ioannou, Ioanna, Chatziantoniou, Angeliki, Drenios, Constantinos, Christodoulou, Panayiota, Kourti, Malamati, Zaravinos, Apostolos
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10094846/
https://www.ncbi.nlm.nih.gov/pubmed/37047552
http://dx.doi.org/10.3390/ijms24076577
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author Ioannou, Ioanna
Chatziantoniou, Angeliki
Drenios, Constantinos
Christodoulou, Panayiota
Kourti, Malamati
Zaravinos, Apostolos
author_facet Ioannou, Ioanna
Chatziantoniou, Angeliki
Drenios, Constantinos
Christodoulou, Panayiota
Kourti, Malamati
Zaravinos, Apostolos
author_sort Ioannou, Ioanna
collection PubMed
description There are several studies on the deregulated gene expression profiles in kidney cancer, with varying results depending on the tumor histology and other parameters. None of these, however, have identified the networks that the co-deregulated genes (co-DEGs), across different studies, create. Here, we reanalyzed 10 Gene Expression Omnibus (GEO) studies to detect and annotate co-deregulated signatures across different subtypes of kidney cancer or in single-gene perturbation experiments in kidney cancer cells and/or tissue. Using a systems biology approach, we aimed to decipher the networks they form along with their upstream regulators. Differential expression and upstream regulators, including transcription factors [MYC proto-oncogene (MYC), CCAAT enhancer binding protein delta (CEBPD), RELA proto-oncogene, NF-kB subunit (RELA), zinc finger MIZ-type containing 1 (ZMIZ1), negative elongation factor complex member E (NELFE) and Kruppel-like factor 4 (KLF4)] and protein kinases [Casein kinase 2 alpha 1 (CSNK2A1), mitogen-activated protein kinases 1 (MAPK1) and 14 (MAPK14), Sirtuin 1 (SIRT1), Cyclin dependent kinases 1 (CDK1) and 4 (CDK4), Homeodomain interacting protein kinase 2 (HIPK2) and Extracellular signal-regulated kinases 1 and 2 (ERK1/2)], were computed using the Characteristic Direction, as well as GEO2Enrichr and X2K, respectively, and further subjected to GO and KEGG pathways enrichment analyses. Furthermore, using CMap, DrugMatrix and the LINCS L1000 chemical perturbation databases, we highlight putative repurposing drugs, including Etoposide, Haloperidol, BW-B70C, Triamterene, Chlorphenesin, BRD-K79459005 and β-Estradiol 3-benzoate, among others, that may reverse the expression of the identified co-DEGs in kidney cancers. Of these, the cytotoxic effects of Etoposide, Catecholamine, Cyclosporin A, BW-B70C and Lasalocid sodium were validated in vitro. Overall, we identified critical co-DEGs across different subtypes in kidney cancer, and our results provide an innovative framework for their potential use in the future.
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spelling pubmed-100948462023-04-13 Signatures of Co-Deregulated Genes and Their Transcriptional Regulators in Kidney Cancers Ioannou, Ioanna Chatziantoniou, Angeliki Drenios, Constantinos Christodoulou, Panayiota Kourti, Malamati Zaravinos, Apostolos Int J Mol Sci Article There are several studies on the deregulated gene expression profiles in kidney cancer, with varying results depending on the tumor histology and other parameters. None of these, however, have identified the networks that the co-deregulated genes (co-DEGs), across different studies, create. Here, we reanalyzed 10 Gene Expression Omnibus (GEO) studies to detect and annotate co-deregulated signatures across different subtypes of kidney cancer or in single-gene perturbation experiments in kidney cancer cells and/or tissue. Using a systems biology approach, we aimed to decipher the networks they form along with their upstream regulators. Differential expression and upstream regulators, including transcription factors [MYC proto-oncogene (MYC), CCAAT enhancer binding protein delta (CEBPD), RELA proto-oncogene, NF-kB subunit (RELA), zinc finger MIZ-type containing 1 (ZMIZ1), negative elongation factor complex member E (NELFE) and Kruppel-like factor 4 (KLF4)] and protein kinases [Casein kinase 2 alpha 1 (CSNK2A1), mitogen-activated protein kinases 1 (MAPK1) and 14 (MAPK14), Sirtuin 1 (SIRT1), Cyclin dependent kinases 1 (CDK1) and 4 (CDK4), Homeodomain interacting protein kinase 2 (HIPK2) and Extracellular signal-regulated kinases 1 and 2 (ERK1/2)], were computed using the Characteristic Direction, as well as GEO2Enrichr and X2K, respectively, and further subjected to GO and KEGG pathways enrichment analyses. Furthermore, using CMap, DrugMatrix and the LINCS L1000 chemical perturbation databases, we highlight putative repurposing drugs, including Etoposide, Haloperidol, BW-B70C, Triamterene, Chlorphenesin, BRD-K79459005 and β-Estradiol 3-benzoate, among others, that may reverse the expression of the identified co-DEGs in kidney cancers. Of these, the cytotoxic effects of Etoposide, Catecholamine, Cyclosporin A, BW-B70C and Lasalocid sodium were validated in vitro. Overall, we identified critical co-DEGs across different subtypes in kidney cancer, and our results provide an innovative framework for their potential use in the future. MDPI 2023-03-31 /pmc/articles/PMC10094846/ /pubmed/37047552 http://dx.doi.org/10.3390/ijms24076577 Text en © 2023 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
Ioannou, Ioanna
Chatziantoniou, Angeliki
Drenios, Constantinos
Christodoulou, Panayiota
Kourti, Malamati
Zaravinos, Apostolos
Signatures of Co-Deregulated Genes and Their Transcriptional Regulators in Kidney Cancers
title Signatures of Co-Deregulated Genes and Their Transcriptional Regulators in Kidney Cancers
title_full Signatures of Co-Deregulated Genes and Their Transcriptional Regulators in Kidney Cancers
title_fullStr Signatures of Co-Deregulated Genes and Their Transcriptional Regulators in Kidney Cancers
title_full_unstemmed Signatures of Co-Deregulated Genes and Their Transcriptional Regulators in Kidney Cancers
title_short Signatures of Co-Deregulated Genes and Their Transcriptional Regulators in Kidney Cancers
title_sort signatures of co-deregulated genes and their transcriptional regulators in kidney cancers
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10094846/
https://www.ncbi.nlm.nih.gov/pubmed/37047552
http://dx.doi.org/10.3390/ijms24076577
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