MicroRNAs and their target messenger RNAs associated with endometrial carcinogenesis.
Gynecol Oncol
; 110(2): 206-15, 2008 Aug.
Article
em En
| MEDLINE
| ID: mdl-18499237
ABSTRACT
OBJECTIVE:
Recent advances in gene expression technology have provided insights into global messenger RNA (mRNA) expression changes associated with endometrial cancer development. However, the post-transcriptional events that may also have phenotypic consequences remain to be completely delineated. MicroRNAs (miRNAs) are small non-coding RNA transcripts, that influence cell function via modulation of post-transcriptional activity of multiple target mRNA genes. Although recent reports suggest that miRNAs may influence human cancer development, their role in endometrial carcinogenesis remains to be described.METHODS:
We measured expression of 335 unique human miRNAs in 61 fresh-frozen endometrial specimens, including 37 endometrial cancers, 20 normal endometrium, and 4 complex atypical hyperplasia samples. In parallel, expression of 22,000 mRNA genes was analyzed using the Affymetrix Human U133A GeneChips in 29 of the endometrial samples, including 20 endometrial carcinomas and 9 normal endometrial samples. Differentially expressed mRNAs, miRNAs, and predicted miRNA-mRNA targets were integrated and evaluated for representation of relevant functional biologic pathways.RESULTS:
Thirteen miRNAs (p<0.02) and 90 mRNAs (FDR; 0%) were identified to be associated with endometrial cancer development. Twenty-six of the 90 (29%) differentially expressed mRNAs are Sangar-database predicted mRNA targets of the 13 miRNAs. Pathway analysis demonstrates significant involvement of these 26 mRNA genes in processes including cell death, growth, proliferation, and carcinogenesis.CONCLUSION:
We have identified miRNAs and mRNAs associated with endometrial cancer development. Further, our strategy of integrating miRNA/mRNA data may also aid in the identification of important biologic pathways and additional unique genes that have importance in endometrial pathogenesis.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
RNA Mensageiro
/
Transformação Celular Neoplásica
/
Neoplasias do Endométrio
/
MicroRNAs
Tipo de estudo:
Risk_factors_studies
Limite:
Female
/
Humans
Idioma:
En
Ano de publicação:
2008
Tipo de documento:
Article