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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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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0162584</identifier><identifier>PMID: 27612152</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>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</subject><ispartof>PloS one, 2016-09, Vol.11 (9), p.e0162584-e0162584</ispartof><rights>COPYRIGHT 2016 Public Library of Science</rights><rights>2016 Yanaihara et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2016 Yanaihara et al 2016 Yanaihara et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c791t-65734e88f9e6b86d70a80f08bca4eb068ac56d217a827cc97f68bab85bbe0fba3</citedby><cites>FETCH-LOGICAL-c791t-65734e88f9e6b86d70a80f08bca4eb068ac56d217a827cc97f68bab85bbe0fba3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5017778/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5017778/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,725,778,782,862,883,2098,2917,23849,27907,27908,53774,53776,79351,79352</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27612152$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Guan, Xin-Yuan</contributor><creatorcontrib>Yanaihara, Nozomu</creatorcontrib><creatorcontrib>Noguchi, Yukiko</creatorcontrib><creatorcontrib>Saito, Misato</creatorcontrib><creatorcontrib>Takenaka, Masataka</creatorcontrib><creatorcontrib>Takakura, Satoshi</creatorcontrib><creatorcontrib>Yamada, Kyosuke</creatorcontrib><creatorcontrib>Okamoto, Aikou</creatorcontrib><title>MicroRNA Gene Expression Signature Driven by miR-9 Overexpression in Ovarian Clear Cell Carcinoma</title><title>PloS one</title><addtitle>PLoS One</addtitle><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.</description><subject>Adenocarcinoma, Clear Cell - genetics</subject><subject>Analysis</subject><subject>Biology and life sciences</subject><subject>Blotting, Western</subject><subject>Cancer</subject><subject>Cancer genetics</subject><subject>Carcinoma</subject><subject>Cell Line, Tumor</subject><subject>Cell Movement - genetics</subject><subject>Cell Movement - physiology</subject><subject>Chemotherapy</subject><subject>Cluster analysis</subject><subject>Clustering</subject><subject>Development and progression</subject><subject>E-cadherin</subject><subject>Female</subject><subject>Gene expression</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Gynecology</subject><subject>Health aspects</subject><subject>Health risk assessment</subject><subject>Humans</subject><subject>In Vitro Techniques</subject><subject>Luciferase</subject><subject>Medical research</subject><subject>Medical schools</subject><subject>Medicine</subject><subject>Medicine and Health Sciences</subject><subject>Mesenchyme</subject><subject>Metastasis</subject><subject>MicroRNA</subject><subject>MicroRNAs</subject><subject>MicroRNAs - genetics</subject><subject>Middle Aged</subject><subject>miRNA</subject><subject>Obstetrics</subject><subject>Ovarian cancer</subject><subject>Ovarian carcinoma</subject><subject>Ovarian Neoplasms - genetics</subject><subject>Pathogenesis</subject><subject>Polymerase chain reaction</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>Reverse transcription</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>Statistical analysis</subject><subject>Studies</subject><subject>Transcription (Genetics)</subject><subject>Tumors</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNk99v0zAQxyMEYmPwHyCIhITgocXOLzsvSFUZo9KgUge8Whf33LpK7M5Oqu2_x6XZaNAeJj_Yunzum_PXd1H0mpIxTRn9tLGdM1CPt9bgmNAiyXn2JDqlZZqMioSkT4_OJ9EL7zeE5CkviufRScIKmtA8OY3gu5bOLn5M4gs0GJ_fbB16r62Jr_TKQNs5jL84vUMTV7dxoxejMp7v0OE_UJsQAafBxNMawcVTrOt4Ck5qYxt4GT1TUHt81e9n0a-v5z-n30aX84vZdHI5kqyk7ajIWZoh56rEouLFkhHgRBFeSciwIgUHmRfLhDLgCZOyZKrgFVQ8ryokqoL0LHp70N3W1oveHS8op5xkJeV5IGYHYmlhI7ZON-BuhQUt_gasWwlwrZY1CkkIU1ySlGcqCyfIeZUSomiwrVC41_rc_62rGlxKNK2DeiA6_GL0WqzsTuSEMsZ4EPjQCzh73aFvRaO9DM6BQdvt604Y56H09BEoLWmShIsG9N1_6MNG9NQKwl21UTaUKPeiYpIxUmY0Z1mgxg9QYS2x0TJ0ndIhPkj4OEgITIs37Qo678XsavF4dv57yL4_YtcIdbv2tu7a0H1-CGYHMLS09w7V_XtQIvZDc-eG2A-N6IcmpL05fsv7pLspSf8A_RIQWQ</recordid><startdate>20160909</startdate><enddate>20160909</enddate><creator>Yanaihara, Nozomu</creator><creator>Noguchi, Yukiko</creator><creator>Saito, Misato</creator><creator>Takenaka, Masataka</creator><creator>Takakura, Satoshi</creator><creator>Yamada, Kyosuke</creator><creator>Okamoto, Aikou</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20160909</creationdate><title>MicroRNA Gene Expression Signature Driven by miR-9 Overexpression in Ovarian Clear Cell Carcinoma</title><author>Yanaihara, Nozomu ; Noguchi, Yukiko ; Saito, Misato ; Takenaka, Masataka ; Takakura, Satoshi ; Yamada, Kyosuke ; Okamoto, Aikou</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c791t-65734e88f9e6b86d70a80f08bca4eb068ac56d217a827cc97f68bab85bbe0fba3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Adenocarcinoma, Clear Cell - 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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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