Dysregulated microRNAs in the pathogenesis and progression of cervical neoplasm.
MicroRNAs (miRNAs) play an important role in a variety of physiological as well as pathophysiological processes, including carcinogenesis. The aim of this study is to identify a distinct miRNA expression signature for cervical intraepithelial neoplasia (CIN) and to unveil individual miRNAs that may be involved in the development of cervical carcinoma. Expression profiling using quantitative real-time RT-PCR of 202 miRNAs was performed on micro-dissected high-grade CIN (CIN 2/3) tissues and compared to normal cervical epithelium. Unsupervised hierarchical clustering of the miRNA expression pattern displayed a distinct separation between the CIN and normal cervical epithelium samples. Supervised analysis identified 12 highly differentially regulated miRNAs, including miR-518a, miR-34b, miR-34c, miR-20b, miR-338, miR-9, miR-512-5p, miR-424, miR-345, miR-10a, miR-193b and miR-203, which distinguished the high-grade CIN specimens from normal cervical epithelium. This miRNA signature was further validated by an independent set of high-grade CIN cases. The same characteristic signature can also be used to distinguish cervical squamous cell carcinoma from normal controls. Target prediction analysis revealed that these dysregulated miRNAs mainly control apoptosis signaling pathways and cell cycle regulation. These findings contribute to understanding the role of microRNAs in the pathogenesis and progression of cervical neoplasm at the molecular level.
Department of Obstetrics and Gynecology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong.
Tak-hong
TH
Cheung
Kwun-nok Mimi
KN
Man
Mei-yung
MY
Yu
So-fan
SF
Yim
Nelson S S
NS
Siu
Keith W K
KW
Lo
Graeme
G
Doran
Raymond R Y
RR
Wong
Vivian W
VW
Wang
David I
DI
Smith
Michael J
MJ
Worley
Ross S
RS
Berkowitz
Tony K H
TK
Chung
Yick-fu
YF
Wong
D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002584:Cervix Uteri / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000473:pathology; D002578:Uterine Cervical Dysplasia / Q000235:genetics* / Q000473:pathology
D035683:MicroRNAs