A childhood acute lymphoblastic leukemia-specific lncRNA implicated in prednisolone resistance, cell proliferation, and migration.
Oncotarget
; 8(5): 7477-7488, 2017 Jan 31.
Article
de En
| MEDLINE
| ID: mdl-27980230
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.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Prednisolone
/
Leucémie-lymphome lymphoblastique à précurseurs B
/
Mouvement cellulaire
/
Résistance aux médicaments antinéoplasiques
/
Prolifération cellulaire
/
ARN long non codant
/
Antinéoplasiques
Type d'étude:
Prognostic_studies
Limites:
Child
/
Child, preschool
/
Female
/
Humans
/
Male
Langue:
En
Journal:
Oncotarget
Année:
2017
Type de document:
Article
Pays d'affiliation:
Canada