MicroRNA Gene Expression Signature Driven by miR-9 Overexpression in Ovarian Clear Cell Carcinoma

PLoS One. 2016 Sep 9;11(9):e0162584. doi: 10.1371/journal.pone.0162584. eCollection 2016.

Abstract

Previous studies have identified microRNA (miRNA) involvement in human cancers. This study aimed to elucidate potential clinical and biological associations of ovarian cancer-related miRNA gene expression profiles in high-grade serous carcinoma (HGSC) and ovarian clear cell carcinoma (OCCC). Accordingly, we investigated 27 patients with ovarian cancer (12 HGSC and 15 OCCC cases) using quantitative real-time reverse transcription polymerase chain reaction to determine the cancer-related miRNA expressions. Gene Cluster 3.0 was used for hierarchical clustering analysis, and differentially expressed miRNAs between HGSC and OCCC were identified by the class comparison analysis using BRB-ArrayTools. An unsupervised hierarchical clustering analysis identified two distinct miRNA expression clusters, with histological subtype-related significant differences in the associations between clusters and clinicopathological features. A comparison of miRNA expression in HGSCs and OCCCs identified five miRNAs (miR-132, miR-9, miR-126, miR-34a, and miR-21), with OCCCs demonstrating a statistically higher expression. Further investigation of the biological significance of miR-9 overexpression in OCCC revealed that miR-9 inhibition reduced the cell invasion ability and upregulated E-cadherin expression. Using a luciferase reporter assay, we further demonstrated the direct binding of miR-9 to E-cadherin. Global cancer-related miRNA expression analysis identified statistically unique profiles that could discriminate ovarian cancer histotypes. In OCCC, miR-9 overexpression may affect pathogenesis by targeting E-cadherin, thereby inducing an epithelial-mesenchymal transition. Therefore, miR-9 may be a promising therapeutic target strategy for OCCC.

MeSH terms

  • Adenocarcinoma, Clear Cell / genetics*
  • Blotting, Western
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Movement / physiology
  • Female
  • Humans
  • In Vitro Techniques
  • MicroRNAs / genetics*
  • Middle Aged
  • Ovarian Neoplasms / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • MIRN126 microRNA, human
  • MIRN132 microRNA, human
  • MIRN34 microRNA, human
  • MIRN92 microRNA, human
  • MicroRNAs

Grants and funding

This study was supported by Japan Society for the Promotion of Science KAKENHI Grant Number 25462615(NY), 25462616(ST), and JP16K11159 (NY) (https://www.jsps.go.jp/j-grantsinaid/) and The Jikei University Research Fund for Graduate Students (YN)(http://j-net.jikei.ac.jp/~daigakuin/H24jyoseikinsaitaku.pdf). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.