Authors: Tak-hong Cheung, Kwun-nok Mimi Man, Mei-yung Yu, So-fan Yim, Nelson S.S. Siu, Keith W.K. Lo, Graeme Doran, Raymond R.Y. Wong, Vivian W. Wang, David I. Smith, Michael J. Worley, Jr., Ross S. Berkowitz, Tony K.H. Chung and Yick-fu Wong

Tak-hong Cheung

Department of Obstetrics and Gynecology; The Chinese University of Hong Kong; Prince of Wales Hospital; Shatin, Hong Kong
These authors contributed equally to this work.

Kwun-nok Mimi Man

Department of Obstetrics and Gynecology; The Chinese University of Hong Kong; Prince of Wales Hospital; Shatin, Hong Kong; These authors contributed equally to this work

Mei-yung Yu

Department of Anatomical and Cellular Pathology; The Chinese University of Hong Kong; Prince of Wales Hospital; Shatin, Hong Kong

So-fan Yim

Department of Obstetrics and Gynecology; The Chinese University of Hong Kong; Prince of Wales Hospital; Shatin, Hong Kong

Nelson S.S. Siu

Department of Obstetrics and Gynecology; The Chinese University of Hong Kong; Prince of Wales Hospital; Shatin, Hong Kong

Keith W.K. Lo

Department of Obstetrics and Gynecology; The Chinese University of Hong Kong; Prince of Wales Hospital; Shatin, Hong Kong

Graeme Doran

Department of Pathology; Harvard Medical School; Boston, MA USA

Raymond R.Y. Wong

Department of Obstetrics and Gynecology; Brigham and Women’s Hospital; Harvard Medical School; Boston, MA USA

Vivian W. Wang

Department of Pathology and Laboratoty Medicine; Mayo Clinic; Rochester, MN USA

David I. Smith

Department of Pathology and Laboratoty Medicine; Mayo Clinic; Rochester, MN USA

Michael J. Worley, Jr.

Department of Obstetrics and Gynecology; Brigham and Women’s Hospital; Harvard Medical School; Boston, MA USA

Ross S. Berkowitz

Department of Obstetrics and Gynecology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA

Tony K.H. Chung

Department of Obstetrics and Gynecology; The Chinese University of Hong Kong; Prince of Wales Hospital; Shatin, Hong Kong

Yick-fu Wong

Corresponding author: yfwong@rics.bwh.harvard.edu
Department of Obstetrics and Gynecology; The Chinese University of Hong Kong; Prince of Wales Hospital; Shatin, Hong Kong; Department of Obstetrics and Gynecology; Brigham and Women’s Hospital; Harvard Medical School; Boston, MA USA

Abstract:
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.

Received: April 19, 2012; Accepted: June 26, 2012

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