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Long noncoding RNA HIKER regulates erythropoiesis in Monge’s disease via CSNK2B

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dc.contributor.author Azad, Priti
dc.contributor.author Zhou, Dan
dc.contributor.author Tu, Hung-Chi
dc.contributor.author Villafuerte Castrillón, Francisco Carlos
dc.contributor.author Traver, David
dc.contributor.author Rana, Tariq M.
dc.contributor.author Haddad, Gabriel G.
dc.coverage.spatial Cerro de Pasco, Pasco, Perú
dc.date.accessioned 2023-04-16T04:38:15Z
dc.date.available 2023-04-16T04:38:15Z
dc.date.issued 2023
dc.identifier.uri https://hdl.handle.net/20.500.12866/13389
dc.description.abstract Excessive Erythrocytosis (EE) is a major hallmark of patients suffering from chronic mountain sickness (CMS, Monge's disease) and is responsible for major morbidity and even mortality in early adulthood. We took advantage of unique populations, one living at high altitude (Peru) showing EE, while another population, at the same altitude and region, shows no evidence of EE (non-CMS). Through RNA-seq, we identified and validated the function of a group of long non-coding RNA (lncRNAs) that regulate erythropoiesis in Monge's disease but not in the non-CMS population. Among these lncRNAs is HIKER (Hypoxia Induced Kinase-mediated Erythropoietic Regulator)/LINC02228 which we showed plays a critical role in erythropoiesis in CMS cells. Under hypoxia, HIKER modulated CSNK2B (the regulatory subunit of Casein kinase 2). A down-regulation of HIKER down-regulated CSNK2B, remarkably reducing erythropoiesis (<70% reduction of BFUs); furthermore, an up-regulation of CSNK2B on the background of HIKER down-regulation rescued erythropoiesis defects. Pharmacologic inhibition of CSNK2B drastically reduced erythroid colonies (50-75% reduction in BFU colonies) and knock-down of CSNK2B in zebrafish lead to a defect in hemoglobinization (<97% morphants show reduction in hemoglobin levels). We conclude that HIKER regulates erythropoiesis in Monge's disease and acts through at least one specific target, CSNK2B, a casein kinase. en_US
dc.language.iso eng
dc.publisher American Society for Clinical Investigation
dc.relation.ispartofseries Journal of Clinical Investigation
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
dc.subject Hypoxia en_US
dc.subject Genetics en_US
dc.subject Hematology en_US
dc.subject Noncoding RNAs en_US
dc.title Long noncoding RNA HIKER regulates erythropoiesis in Monge’s disease via CSNK2B en_US
dc.type info:eu-repo/semantics/article
dc.identifier.doi https://doi.org/10.1172/jci165831
dc.relation.issn 1558-8238


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