Meta-analysis of gene signatures and key pathways indicates suppression of JNK pathway as a regulator of chemo-resistance in AML

Abstract The pathways and robust deregulated gene signatures involved in AML chemo-resistance are not fully understood. Multiple subgroups of AMLs which are under treatment of various regimens seem to have similar regulatory gene(s) or pathway(s) related to their chemo-resistance phenotype. In this...

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Autores principales:	Parastoo Modarres, Farzaneh Mohamadi Farsani, Amir Abas Nekouie, Sadeq Vallian
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a59b6b2f338847b0a12172c886070653
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spelling	oai:doaj.org-article:a59b6b2f338847b0a12172c8860706532021-12-02T16:04:26ZMeta-analysis of gene signatures and key pathways indicates suppression of JNK pathway as a regulator of chemo-resistance in AML10.1038/s41598-021-91864-22045-2322https://doaj.org/article/a59b6b2f338847b0a12172c8860706532021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-91864-2https://doaj.org/toc/2045-2322Abstract The pathways and robust deregulated gene signatures involved in AML chemo-resistance are not fully understood. Multiple subgroups of AMLs which are under treatment of various regimens seem to have similar regulatory gene(s) or pathway(s) related to their chemo-resistance phenotype. In this study using gene set enrichment approach, deregulated genes and pathways associated with relapse after chemotherapy were investigated in AML samples. Five AML libraries compiled from GEO and ArrayExpress repositories were used to identify significantly differentially expressed genes between chemo-resistance and chemo-sensitive groups. Functional and pathway enrichment analysis of differentially expressed genes was performed to assess molecular mechanisms related to AML chemotherapeutic resistance. A total of 34 genes selected to be differentially expressed in the chemo-resistance compared to the chemo-sensitive group. Among the genes selected, c-Jun, AKT3, ARAP3, GABBR1, PELI2 and SORT1 are involved in neurotrophin, estrogen, cAMP and Toll-like receptor signaling pathways. All these pathways are located upstream and regulate JNK signaling pathway which functions as a key regulator of cellular apoptosis. Our expression data are in favor of suppression of JNK pathway, which could induce pro-apoptotic gene expression as well as down regulation of survival factors, introducing this pathway as a key regulator of drug-resistance development in AML.Parastoo ModarresFarzaneh Mohamadi FarsaniAmir Abas NekouieSadeq VallianNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-16 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Parastoo Modarres Farzaneh Mohamadi Farsani Amir Abas Nekouie Sadeq Vallian Meta-analysis of gene signatures and key pathways indicates suppression of JNK pathway as a regulator of chemo-resistance in AML
description	Abstract The pathways and robust deregulated gene signatures involved in AML chemo-resistance are not fully understood. Multiple subgroups of AMLs which are under treatment of various regimens seem to have similar regulatory gene(s) or pathway(s) related to their chemo-resistance phenotype. In this study using gene set enrichment approach, deregulated genes and pathways associated with relapse after chemotherapy were investigated in AML samples. Five AML libraries compiled from GEO and ArrayExpress repositories were used to identify significantly differentially expressed genes between chemo-resistance and chemo-sensitive groups. Functional and pathway enrichment analysis of differentially expressed genes was performed to assess molecular mechanisms related to AML chemotherapeutic resistance. A total of 34 genes selected to be differentially expressed in the chemo-resistance compared to the chemo-sensitive group. Among the genes selected, c-Jun, AKT3, ARAP3, GABBR1, PELI2 and SORT1 are involved in neurotrophin, estrogen, cAMP and Toll-like receptor signaling pathways. All these pathways are located upstream and regulate JNK signaling pathway which functions as a key regulator of cellular apoptosis. Our expression data are in favor of suppression of JNK pathway, which could induce pro-apoptotic gene expression as well as down regulation of survival factors, introducing this pathway as a key regulator of drug-resistance development in AML.
format	article
author	Parastoo Modarres Farzaneh Mohamadi Farsani Amir Abas Nekouie Sadeq Vallian
author_facet	Parastoo Modarres Farzaneh Mohamadi Farsani Amir Abas Nekouie Sadeq Vallian
author_sort	Parastoo Modarres
title	Meta-analysis of gene signatures and key pathways indicates suppression of JNK pathway as a regulator of chemo-resistance in AML
title_short	Meta-analysis of gene signatures and key pathways indicates suppression of JNK pathway as a regulator of chemo-resistance in AML
title_full	Meta-analysis of gene signatures and key pathways indicates suppression of JNK pathway as a regulator of chemo-resistance in AML
title_fullStr	Meta-analysis of gene signatures and key pathways indicates suppression of JNK pathway as a regulator of chemo-resistance in AML
title_full_unstemmed	Meta-analysis of gene signatures and key pathways indicates suppression of JNK pathway as a regulator of chemo-resistance in AML
title_sort	meta-analysis of gene signatures and key pathways indicates suppression of jnk pathway as a regulator of chemo-resistance in aml
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/a59b6b2f338847b0a12172c886070653
work_keys_str_mv	AT parastoomodarres metaanalysisofgenesignaturesandkeypathwaysindicatessuppressionofjnkpathwayasaregulatorofchemoresistanceinaml AT farzanehmohamadifarsani metaanalysisofgenesignaturesandkeypathwaysindicatessuppressionofjnkpathwayasaregulatorofchemoresistanceinaml AT amirabasnekouie metaanalysisofgenesignaturesandkeypathwaysindicatessuppressionofjnkpathwayasaregulatorofchemoresistanceinaml AT sadeqvallian metaanalysisofgenesignaturesandkeypathwaysindicatessuppressionofjnkpathwayasaregulatorofchemoresistanceinaml
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Meta-analysis of gene signatures and key pathways indicates suppression of JNK pathway as a regulator of chemo-resistance in AML

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