MicroRNAs and their target messenger RNAs associated with endometrial carcinogenesis.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Boren, T; Xiong, Y; Hakam, A; Wenham, R; Apte, S; Wei, Z; Kamath, S; Chen, D-T; Dressman, H; Lancaster, JM

Published Date

  • August 2008

Published In

Volume / Issue

  • 110 / 2

Start / End Page

  • 206 - 215

PubMed ID

  • 18499237

Pubmed Central ID

  • 18499237

Electronic International Standard Serial Number (EISSN)

  • 1095-6859

Digital Object Identifier (DOI)

  • 10.1016/j.ygyno.2008.03.023

Language

  • eng

Conference Location

  • United States