MicroRNAs and their target messenger RNAs associated with endometrial carcinogenesis.
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.


CONCLUSIONS
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.
Boren
Todd
T
H. Lee Moffitt Cancer Center & Research Institute, Divisions of Gynecologic Surgical Oncology, Tampa, FL 33612, USA. Todd.Boren@moffitt.org
Xiong
Yin
Y
Hakam
Ardeshir
A
Wenham
Robert
R
Apte
Sachin
S
Wei
ZhengZheng
Z
Kamath
Siddharth
S
Chen
Dung-Tsa
DT
Dressman
Holly
H
Lancaster
Johnathan M
JM
D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D015870:Gene Expression; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics* / Q000302:isolation & purification; D009367:Neoplasm Staging; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics* / Q000302:isolation & purification; D020133:Reverse Transcriptase Polymerase Chain Reaction
D035683:MicroRNAs; D012333:RNA, Messenger