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

Zhaojian Liu, Jinsong Liu, Miguel F. Segura, Changshun Shao, Peng Lee, Yaoqin Gong, Eva Hernando, Jian Jun Wei*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

117 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)204-215
Number of pages12
JournalJournal of Pathology
Volume228
Issue number2
DOIs
StatePublished - Oct 2012

Keywords

  • BRCA1
  • HMGA2
  • MTSS1
  • miR-182
  • ovarian serous carcinoma

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Fingerprint Dive into the research topics of 'MiR-182 overexpression in tumourigenesis of high-grade serous ovarian carcinoma'. Together they form a unique fingerprint.

Cite this