MicroRNA Gene Expression Signature Driven by miR-9 Overexpression in Ovarian Clear Cell Carcinoma.
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.
Department of Obstetrics and Gynecology, The Jikei University School of Medicine, Tokyo, Japan.
Nozomu
N
Yanaihara
Department of Obstetrics and Gynecology, The Jikei University School of Medicine, Tokyo, Japan.
Yukiko
Y
Noguchi
Department of Obstetrics and Gynecology, The Jikei University School of Medicine, Tokyo, Japan.
Misato
M
Saito
Department of Obstetrics and Gynecology, The Jikei University School of Medicine, Tokyo, Japan.
Masataka
M
Takenaka
Department of Obstetrics and Gynecology, Dokkyo Medical University Koshigaya Hospital, Saitama, Japan.
Satoshi
S
Takakura
Department of Obstetrics and Gynecology, The Jikei University School of Medicine, Tokyo, Japan.
Kyosuke
K
Yamada
Department of Obstetrics and Gynecology, The Jikei University School of Medicine, Tokyo, Japan.
Aikou
A
Okamoto
D018262:Adenocarcinoma, Clear Cell / Q000235:genetics*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics / Q000502:physiology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
C527111:MIRN126 microRNA, human; C547077:MIRN132 microRNA, human; C522425:MIRN34 microRNA, human; C541874:MIRN92 microRNA, human; D035683:MicroRNAs