title: A childhood acute lymphoblastic leukemia-specific lncRNA implicated in prednisolone resistance, cell proliferation, and migration.
abstract: Childhood acute lymphoblastic leukemia (cALL) is the most common pediatric cancer and, despite an 85% cure rate, still represents a major cause of disease-related death in children. Recent studies have implicated long non-coding RNAs (lncRNAs) in cALL etiology, progression, and treatment response. However, barring some exceptions little is known about the functional impact of lncRNAs on cancer biology, which limits their potential as potential therapeutic targets. We wanted to investigate the functional role of lncRNAs identified as specifically overexpressed in pre-B cALL by whole-transcriptome sequencing. Here we report five lncRNAs specifically upregulated in pre-B cALL that had significant impacts on cancer hallmark traits such as cell proliferation, migration, apoptosis, and treatment response. In particular, silencing of the RP11-137H2.4 lncRNA effectively restored normal glucocorticoid (GC) response in a GC-resistant pre-B cALL cell line and specifically modulated expression of members of both the NRAS/BRAF/NF-κB MAPK cascade and cell cycle pathways. Since GC form the cornerstone of cALL chemotherapy and resistance in cALL confers a dismal prognosis, characterizing RP11-137H2.4'sexact role and function in this process will be critical to the development of new therapeutic approaches to overcome GC resistance in children treated for cALL.
authors.affiliation: Division of Hematology-Oncology, Research Center, Sainte-Justine University Health Center, Montreal, QC, Canada.
authors.forename: Manon
authors.initials: M
authors.lastname: Ouimet
authors.affiliation: Division of Hematology-Oncology, Research Center, Sainte-Justine University Health Center, Montreal, QC, Canada.
authors.forename: Simon
authors.initials: S
authors.lastname: Drouin
authors.affiliation: Division of Hematology-Oncology, Research Center, Sainte-Justine University Health Center, Montreal, QC, Canada.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Lajoie
authors.affiliation: Division of Hematology-Oncology, Research Center, Sainte-Justine University Health Center, Montreal, QC, Canada.
authors.forename: Maxime
authors.initials: M
authors.lastname: Caron
authors.affiliation: Division of Hematology-Oncology, Research Center, Sainte-Justine University Health Center, Montreal, QC, Canada.
authors.forename: Pascal
authors.initials: P
authors.lastname: St-Onge
authors.affiliation: Division of Hematology-Oncology, Research Center, Sainte-Justine University Health Center, Montreal, QC, Canada.
authors.forename: Romain
authors.initials: R
authors.lastname: Gioia
authors.affiliation: Division of Hematology-Oncology, Research Center, Sainte-Justine University Health Center, Montreal, QC, Canada.
authors.forename: Chantal
authors.initials: C
authors.lastname: Richer
authors.affiliation: Division of Hematology-Oncology, Research Center, Sainte-Justine University Health Center, Montreal, QC, Canada.|Department of Pediatrics, University of Montreal, Montreal, QC, Canada.
authors.forename: Daniel
authors.initials: D
authors.lastname: Sinnett
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002648:Child; D002675:Child, Preschool; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011239:Prednisolone / Q000494:pharmacology*; D034622:RNA Interference; D062085:RNA, Long Noncoding / Q000235:genetics* / Q000378:metabolism; D013997:Time Factors; D014162:Transfection
chemical_list: D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D062085:RNA, Long Noncoding; C000626390:long noncoding RNA RP11-137H2.4, human; D011239:Prednisolone
keywords: RNASeq; acute lymphoblastic leukemia; glucocorticoids; long non-coding RNA; treatment resistance