Dual biomarkers long non-coding RNA GAS5 and its target, NR3C1, contribute to acute myeloid leukemia.
Adolescent
Adult
Aged
Aged, 80 and over
Alleles
Child
Child, Preschool
Female
Genetic Association Studies
Genetic Predisposition to Disease
Genotype
Haplotypes
/ genetics
Humans
Iran
/ epidemiology
Leukemia, Myeloid
/ genetics
Male
Middle Aged
Polymorphism, Single Nucleotide
/ genetics
RNA, Long Noncoding
/ genetics
Receptors, Glucocorticoid
/ genetics
AML
GAS5
NR3C1
Polymorphism
lncRNA
Journal
Experimental and molecular pathology
ISSN: 1096-0945
Titre abrégé: Exp Mol Pathol
Pays: Netherlands
ID NLM: 0370711
Informations de publication
Date de publication:
06 2020
06 2020
Historique:
received:
01
01
2020
accepted:
04
02
2020
pubmed:
8
2
2020
medline:
28
10
2020
entrez:
8
2
2020
Statut:
ppublish
Résumé
Acute myeloid leukemia (AML) is a complex hematological neoplasm with poor prognosis. At present, overwhelming evidence indicates that different genetic abnormalities are relevant to the pathogenesis of AML. Nevertheless, its exact molecular mechanism is still unknown. Recently, it was reported that lncRNAs play crucial roles in tumorigenesis. But, their role in the molecular pathogenesis of AML has not been extensively explored. GAS5, one of the earliest known lncRNAs, has an essential role in the formation and progression of multiple human cancers. It was recently demonstrated that GAS5 acts as a riborepressor of the Glucocorticoid receptor) GR) and abnormal levels of GAS5 may alter response of hematopoietic cells to glucocorticoids. GAS5 can have interaction with the GR that encoded by NR3C1 gene and inhibit its transcriptional activity. To test whether the genetic variants can be associated with AML risk, we genotyped rs55829688 (T > C) polymorphism in GAS5 and three NR3C1 SNPs namely rs6195, rs41423247 and rs6189/rs6190 in a population of 100 Iranian AML patients and 100 healthy subjects. The analysis of the data showed the frequency of alleles and genotypes of rs55829688 and rs6189/rs6190 polymorphisms did not differ between patients and healthy subjects. But, rs41423247 and rs6195 demonstrated a significant correlation with AML risk. The rs6195 was associated with higher AML susceptibility in the co-dominant (OR = 4.58, 95% CI = 2.11-9.981, P < .0001), dominant (OR = 4.55, 95% CI = 2.155-9.613, P < .0001), and over-dominant (OR = 4.43, 95% CI = 2.042-9.621, P < .0001) models. Also, the rs41423247 polymorphism was associated with higher risk of AML in co-dominant (OR = 2.07, 95% CI = 1.171-4.242, P = .012) and dominant (OR = 2.47, 95% CI = 1.192-5.142, P = .010) models. Furthermore, haplotype analysis (rs41423247, rs6189.rs6190, rs6195, and rs55829688 respectively) demonstrated that GGAT, CGGT, and GGGT haplotypes were associated with higher risk of AML in the studied population (p-values = .007, 0.042 and 0.044, respectively). The present study reveals a possible role for NR3C1 in the pathogenesis of AML.
Identifiants
pubmed: 32032633
pii: S0014-4800(20)30002-2
doi: 10.1016/j.yexmp.2020.104399
pii:
doi:
Substances chimiques
GAS5 long non-coding RNA, human
0
NR3C1 protein, human
0
RNA, Long Noncoding
0
Receptors, Glucocorticoid
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
104399Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.