A Variant in a MicroRNA complementary site in the 3' UTR of the KIT oncogene increases risk of acral melanoma.
Oncogene
; 30(13): 1542-50, 2011 Mar 31.
Article
en En
| MEDLINE
| ID: mdl-21119596
ABSTRACT
MicroRNAs (miRNAs) are small â¼22nt single stranded RNAs that negatively regulate protein expression by binding to partially complementary sequences in the 3' untranslated region (3' UTRs) of target gene messenger RNAs (mRNA). Recently, mutations have been identified in both miRNAs and target genes that disrupt regulatory relationships, contribute to oncogenesis and serve as biomarkers for cancer risk. KIT, an established oncogene with a multifaceted role in melanogenesis and melanoma pathogenesis, has recently been shown to be upregulated in some melanomas, and is also a target of the miRNA miR-221. Here, we describe a genetic variant in the 3' UTR of the KIT oncogene that correlates with a greater than fourfold increased risk of acral melanoma. This KIT variant results in a mismatch in the seed region of a miR-221 complementary site and reporter data suggests that this mismatch can result in increased expression of the KIT oncogene. Consistent with the hypothesis that this is a functional variant, KIT mRNA and protein levels are both increased in the majority of samples harboring the KIT variant. This work identifies a novel genetic marker for increased heritable risk of melanoma.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Oncogenes
/
Neoplasias Cutáneas
/
Proteínas Proto-Oncogénicas c-kit
/
Regiones no Traducidas 3'
/
MicroARNs
/
Melanoma
Tipo de estudio:
Etiology_studies
/
Observational_studies
/
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Oncogene
Asunto de la revista:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Año:
2011
Tipo del documento:
Article
País de afiliación:
Estados Unidos