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). Accordi...

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Veröffentlicht in:PloS one 2016-09, Vol.11 (9), p.e0162584-e0162584
Hauptverfasser: Yanaihara, Nozomu, Noguchi, Yukiko, Saito, Misato, Takenaka, Masataka, Takakura, Satoshi, Yamada, Kyosuke, Okamoto, Aikou
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container_issue 9
container_start_page e0162584
container_title PloS one
container_volume 11
creator Yanaihara, Nozomu
Noguchi, Yukiko
Saito, Misato
Takenaka, Masataka
Takakura, Satoshi
Yamada, Kyosuke
Okamoto, Aikou
description 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.
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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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>27612152</pmid><doi>10.1371/journal.pone.0162584</doi><tpages>e0162584</tpages><oa>free_for_read</oa></addata></record>
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subjects Adenocarcinoma, Clear Cell - genetics
Analysis
Biology and life sciences
Blotting, Western
Cancer
Cancer genetics
Carcinoma
Cell Line, Tumor
Cell Movement - genetics
Cell Movement - physiology
Chemotherapy
Cluster analysis
Clustering
Development and progression
E-cadherin
Female
Gene expression
Genes
Genetic aspects
Gynecology
Health aspects
Health risk assessment
Humans
In Vitro Techniques
Luciferase
Medical research
Medical schools
Medicine
Medicine and Health Sciences
Mesenchyme
Metastasis
MicroRNA
MicroRNAs
MicroRNAs - genetics
Middle Aged
miRNA
Obstetrics
Ovarian cancer
Ovarian carcinoma
Ovarian Neoplasms - genetics
Pathogenesis
Polymerase chain reaction
Reverse Transcriptase Polymerase Chain Reaction
Reverse transcription
Ribonucleic acid
RNA
Statistical analysis
Studies
Transcription (Genetics)
Tumors
title MicroRNA Gene Expression Signature Driven by miR-9 Overexpression in Ovarian Clear Cell Carcinoma
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