MiR-182 overexpression in tumourigenesis of high-grade serous ovarian carcinoma

J Pathol. 2012 Oct;228(2):204-15. doi: 10.1002/path.4000. Epub 2012 Apr 18.


Molecular pathogenesis of high-grade serous ovarian carcinoma (HG-SOC) is poorly understood. Recent recognition of HG-SOC precursor lesions, defined as serous tubal intraepithelial carcinoma (STIC) in fimbria, provides a new venue for the study of early genetic changes in HG-SOC. Using microRNA profiling analysis, we found that miR-182 expression was significantly higher in STIC than in matched normal Fallopian tube. Further study revealed that miR-182 was significantly overexpressed in most HG-SOC cases. To test whether miR-182 plays a major role in early tumourigenesis of HG-SOC, we overexpressed miR-182 in immortalized ovarian surface, Fallopian tube secretory cells and malignant ovarian cell lines, and found that miR-182 overexpression resulted in increased tumour transformation in vitro, and enhanced tumour invasiveness in vitro and metastasis in vivo. Mechanistically, we demonstrated that the oncogenic properties of miR-182 in ovarian cancer were mediated in part by its impaired repair of DNA double-strand breaks and negative regulation of breast cancer 1 (BRCA1) and metastasis suppressor 1 (MTSS1) expression as well as its positive regulation of the oncogene high-mobility group AT-hook 2 (HMGA2). Our findings suggest that miR-182 dysregulation confers powerful oncogenic potential in the tumourigenesis of HG-SOC. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • BRCA1 Protein / genetics
  • Cell Line, Transformed
  • Cell Line, Tumor
  • Cell Transformation, Neoplastic / genetics
  • Collagen
  • Cystadenocarcinoma, Serous / genetics*
  • Cystadenocarcinoma, Serous / pathology
  • DNA Damage
  • DNA Repair / genetics
  • Drug Combinations
  • Female
  • Gene Expression Regulation, Neoplastic*
  • HMGA2 Protein / genetics
  • Humans
  • Laminin
  • MicroRNAs / genetics*
  • Microfilament Proteins / genetics
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology
  • Neoplasm Proteins / genetics
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / pathology
  • Proteoglycans
  • Retrospective Studies
  • Tissue Array Analysis
  • Tumor Stem Cell Assay / methods
  • Up-Regulation*


  • BRCA1 Protein
  • BRCA1 protein, human
  • Drug Combinations
  • HMGA2 Protein
  • Laminin
  • MTSS1 protein, human
  • MicroRNAs
  • Microfilament Proteins
  • Mirn182 microRNA, human
  • Neoplasm Proteins
  • Proteoglycans
  • matrigel
  • Collagen