Differential Gene Expression in Host Ubiquitination Processes in Childhood Malarial Anemia

Background: Malaria remains one of the leading global causes of childhood morbidity and mortality. In holoendemic Plasmodium falciparum transmission regions, such as western Kenya, severe malarial anemia [SMA, hemoglobin (Hb) < 6.0 g/dl] is the primary form of severe disease. Ubiquitination i...

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Autores principales:	Samuel B. Anyona, Evans Raballah, Qiuying Cheng, Ivy Hurwitz, Caroline Ndege, Elly Munde, Walter Otieno, Philip D. Seidenberg, Kristan A. Schneider, Christophe G. Lambert, Benjamin H. McMahon, Collins Ouma, Douglas J. Perkins
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	ubiquitination ubiquitin proteasome system differential gene expression Plasmodium falciparum malarial anemia Genetics QH426-470
Acceso en línea:	https://doaj.org/article/6736fdb815e94c4c836322c6f4f29425
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spelling	oai:doaj.org-article:6736fdb815e94c4c836322c6f4f294252021-11-22T07:15:58ZDifferential Gene Expression in Host Ubiquitination Processes in Childhood Malarial Anemia1664-802110.3389/fgene.2021.764759https://doaj.org/article/6736fdb815e94c4c836322c6f4f294252021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fgene.2021.764759/fullhttps://doaj.org/toc/1664-8021Background: Malaria remains one of the leading global causes of childhood morbidity and mortality. In holoendemic Plasmodium falciparum transmission regions, such as western Kenya, severe malarial anemia [SMA, hemoglobin (Hb) < 6.0 g/dl] is the primary form of severe disease. Ubiquitination is essential for regulating intracellular processes involved in innate and adaptive immunity. Although dysregulation in ubiquitin molecular processes is central to the pathogenesis of multiple human diseases, the expression patterns of ubiquitination genes in SMA remain unexplored.Methods: To examine the role of the ubiquitination processes in pathogenesis of SMA, differential gene expression profiles were determined in Kenyan children (n = 44, aged <48 mos) with either mild malarial anemia (MlMA; Hb ≥9.0 g/dl; n = 23) or SMA (Hb <6.0 g/dl; n = 21) using the Qiagen Human Ubiquitination Pathway RT2 Profiler PCR Array containing a set of 84 human ubiquitination genes.Results: In children with SMA, 10 genes were down-regulated (BRCC3, FBXO3, MARCH5, RFWD2, SMURF2, UBA6, UBE2A, UBE2D1, UBE2L3, UBR1), and five genes were up-regulated (MDM2, PARK2, STUB1, UBE2E3, UBE2M). Enrichment analyses revealed Ubiquitin-Proteasomal Proteolysis as the top disrupted process, along with altered sub-networks involved in proteasomal, protein, and ubiquitin-dependent catabolic processes.Conclusion: Collectively, these novel results show that protein coding genes of the ubiquitination processes are involved in the pathogenesis of SMA.Samuel B. AnyonaSamuel B. AnyonaEvans RaballahEvans RaballahQiuying ChengIvy HurwitzCaroline NdegeElly MundeElly MundeWalter OtienoPhilip D. SeidenbergKristan A. SchneiderChristophe G. LambertBenjamin H. McMahonCollins OumaCollins OumaDouglas J. PerkinsDouglas J. PerkinsFrontiers Media S.A.articleubiquitinationubiquitin proteasome systemdifferential gene expressionPlasmodium falciparummalarial anemiaGeneticsQH426-470ENFrontiers in Genetics, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	ubiquitination ubiquitin proteasome system differential gene expression Plasmodium falciparum malarial anemia Genetics QH426-470
spellingShingle	ubiquitination ubiquitin proteasome system differential gene expression Plasmodium falciparum malarial anemia Genetics QH426-470 Samuel B. Anyona Samuel B. Anyona Evans Raballah Evans Raballah Qiuying Cheng Ivy Hurwitz Caroline Ndege Elly Munde Elly Munde Walter Otieno Philip D. Seidenberg Kristan A. Schneider Christophe G. Lambert Benjamin H. McMahon Collins Ouma Collins Ouma Douglas J. Perkins Douglas J. Perkins Differential Gene Expression in Host Ubiquitination Processes in Childhood Malarial Anemia
description	Background: Malaria remains one of the leading global causes of childhood morbidity and mortality. In holoendemic Plasmodium falciparum transmission regions, such as western Kenya, severe malarial anemia [SMA, hemoglobin (Hb) < 6.0 g/dl] is the primary form of severe disease. Ubiquitination is essential for regulating intracellular processes involved in innate and adaptive immunity. Although dysregulation in ubiquitin molecular processes is central to the pathogenesis of multiple human diseases, the expression patterns of ubiquitination genes in SMA remain unexplored.Methods: To examine the role of the ubiquitination processes in pathogenesis of SMA, differential gene expression profiles were determined in Kenyan children (n = 44, aged <48 mos) with either mild malarial anemia (MlMA; Hb ≥9.0 g/dl; n = 23) or SMA (Hb <6.0 g/dl; n = 21) using the Qiagen Human Ubiquitination Pathway RT2 Profiler PCR Array containing a set of 84 human ubiquitination genes.Results: In children with SMA, 10 genes were down-regulated (BRCC3, FBXO3, MARCH5, RFWD2, SMURF2, UBA6, UBE2A, UBE2D1, UBE2L3, UBR1), and five genes were up-regulated (MDM2, PARK2, STUB1, UBE2E3, UBE2M). Enrichment analyses revealed Ubiquitin-Proteasomal Proteolysis as the top disrupted process, along with altered sub-networks involved in proteasomal, protein, and ubiquitin-dependent catabolic processes.Conclusion: Collectively, these novel results show that protein coding genes of the ubiquitination processes are involved in the pathogenesis of SMA.
format	article
author	Samuel B. Anyona Samuel B. Anyona Evans Raballah Evans Raballah Qiuying Cheng Ivy Hurwitz Caroline Ndege Elly Munde Elly Munde Walter Otieno Philip D. Seidenberg Kristan A. Schneider Christophe G. Lambert Benjamin H. McMahon Collins Ouma Collins Ouma Douglas J. Perkins Douglas J. Perkins
author_facet	Samuel B. Anyona Samuel B. Anyona Evans Raballah Evans Raballah Qiuying Cheng Ivy Hurwitz Caroline Ndege Elly Munde Elly Munde Walter Otieno Philip D. Seidenberg Kristan A. Schneider Christophe G. Lambert Benjamin H. McMahon Collins Ouma Collins Ouma Douglas J. Perkins Douglas J. Perkins
author_sort	Samuel B. Anyona
title	Differential Gene Expression in Host Ubiquitination Processes in Childhood Malarial Anemia
title_short	Differential Gene Expression in Host Ubiquitination Processes in Childhood Malarial Anemia
title_full	Differential Gene Expression in Host Ubiquitination Processes in Childhood Malarial Anemia
title_fullStr	Differential Gene Expression in Host Ubiquitination Processes in Childhood Malarial Anemia
title_full_unstemmed	Differential Gene Expression in Host Ubiquitination Processes in Childhood Malarial Anemia
title_sort	differential gene expression in host ubiquitination processes in childhood malarial anemia
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/6736fdb815e94c4c836322c6f4f29425
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Differential Gene Expression in Host Ubiquitination Processes in Childhood Malarial Anemia

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