Dysregulated microRNAs in the pathogenesis and progression of cervical neoplasm

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, Ross S. Berkowitz, Tony K.H. Chung, Yick Fu Wong

Research output: Contribution to journalArticle

78 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2876-2884
Number of pages9
JournalCell Cycle
Volume11
Issue number15
DOIs
StatePublished - Aug 1 2012

Keywords

  • Carcinogenesis
  • Cervical cancer
  • Cervical intraepithelial neoplasia
  • MicroRNA
  • Signature

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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  • Cite this

    Cheung, T. H., Man, K. N. M., Yu, M. Y., Yim, S. F., Siu, N. S. S., Lo, K. W. K., Doran, G., Wong, R. R. Y., Wang, V. W., Smith, D. I., Worley, M. J., Berkowitz, R. S., Chung, T. K. H., & Wong, Y. F. (2012). Dysregulated microRNAs in the pathogenesis and progression of cervical neoplasm. Cell Cycle, 11(15), 2876-2884. https://doi.org/10.4161/cc.21278