MicroRNA-150 predicts a favorable prognosis in patients with epithelial ovarian cancer, and inhibits cell invasion and metastasis by suppressing transcriptional repressor ZEB1
MicroRNA (miR)-150 has been reported to be dramatically downregulated in human epithelial ovarian cancer (EOC) tissues and patients' serum compared to normal controls. This study aimed to investigate clinical significance and molecular mechanisms of miR-150 in EOC. In the current study, quantit...
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| description | MicroRNA (miR)-150 has been reported to be dramatically downregulated in human epithelial ovarian cancer (EOC) tissues and patients' serum compared to normal controls. This study aimed to investigate clinical significance and molecular mechanisms of miR-150 in EOC. In the current study, quantitative real-time PCR analysis showed that miR-150 was significantly downregulated in human EOC tissues compared to normal tissue samples. Then, we demonstrated the significant associations of miR-150 downregulation with aggressive clinicopathological features of EOC patients, including high clinical stage and pathological grade, and shorter overall and progression-free survivals. More importantly, the multivariate analysis identified miR-150 expression as an independent prognostic biomarker in EOC. After that, luciferase reporter assays demonstrated that Zinc Finger E-Box Binding Homeobox 1 (ZEB1), a crucial regulator of epithelial-to-mesenchymal transition (EMT), was a direct target of miR-150 in EOC cells. Moreover, we found that the ectopic expression of miR-150 could efficiently inhibit cell proliferation, invasion and metastasis by suppressing the expression of ZEB1. Furthermore, we also observed a significantly negative correlation between miR-150 and ZEB1 mRNA expression in EOC tissues (rs = -0.45, P |
| doi_str_mv | 10.1371/journal.pone.0103965 |
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This study aimed to investigate clinical significance and molecular mechanisms of miR-150 in EOC. In the current study, quantitative real-time PCR analysis showed that miR-150 was significantly downregulated in human EOC tissues compared to normal tissue samples. Then, we demonstrated the significant associations of miR-150 downregulation with aggressive clinicopathological features of EOC patients, including high clinical stage and pathological grade, and shorter overall and progression-free survivals. More importantly, the multivariate analysis identified miR-150 expression as an independent prognostic biomarker in EOC. After that, luciferase reporter assays demonstrated that Zinc Finger E-Box Binding Homeobox 1 (ZEB1), a crucial regulator of epithelial-to-mesenchymal transition (EMT), was a direct target of miR-150 in EOC cells. Moreover, we found that the ectopic expression of miR-150 could efficiently inhibit cell proliferation, invasion and metastasis by suppressing the expression of ZEB1. Furthermore, we also observed a significantly negative correlation between miR-150 and ZEB1 mRNA expression in EOC tissues (rs = -0.45, P<0.001). In conclusion, these findings offer the convincing evidence that aberrant expression of miR-150 may play a role in tumor progression and prognosis in patients with EOC. Moreover, our data reveal that miR-150 may function as a tumor suppressor and modulate EOC cell proliferation, and invasion by directly and negatively regulating ZEB1, implying the re-expression of miR-150 might be a potential therapeutic strategy for EOC.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0103965</identifier><identifier>PMID: 25090005</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Binding sites ; Biomarkers ; Cancer ; Cancer metastasis ; Cancer therapies ; Carcinoma, Ovarian Epithelial ; Cell growth ; Cell Line, Tumor ; Cell Proliferation ; Colorectal cancer ; Comparative analysis ; Development and progression ; Disease Progression ; Disease-Free Survival ; Down-Regulation ; Ectopic expression ; Female ; Gastric cancer ; Gene expression ; Gene Expression Regulation, Neoplastic ; Genetic aspects ; Gynecology ; Health aspects ; Homeobox ; Homeodomain Proteins - genetics ; Homeodomain Proteins - metabolism ; Hospitals ; Humans ; Kaplan-Meier Estimate ; Luciferase ; Lung cancer ; Lymphoma ; Medical prognosis ; Medical research ; Medicine ; Medicine and Health Sciences ; Mesenchyme ; Metastases ; Metastasis ; MicroRNA ; MicroRNAs ; MicroRNAs - genetics ; MicroRNAs - metabolism ; Middle Aged ; miRNA ; Molecular modelling ; Multivariate Analysis ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Neoplasms, Glandular and Epithelial - genetics ; Neoplasms, Glandular and Epithelial - pathology ; Obstetrics ; Ovarian cancer ; Ovarian carcinoma ; Ovarian Neoplasms - genetics ; Ovarian Neoplasms - pathology ; Patients ; Prognosis ; Real-Time Polymerase Chain Reaction ; Repressor Proteins - metabolism ; Ribonucleic acid ; RNA ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; RNA, Small Interfering - metabolism ; Stomach cancer ; Tissues ; Transcription ; Transcription (Genetics) ; Transcription Factors - genetics ; Transcription Factors - metabolism ; Tumor suppressor genes ; Womens health ; Zinc ; Zinc Finger E-box-Binding Homeobox 1 ; Zinc finger proteins</subject><ispartof>PloS one, 2014-08, Vol.9 (8), p.e103965-e103965</ispartof><rights>COPYRIGHT 2014 Public Library of Science</rights><rights>2014 Jin 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>2014 Jin et al 2014 Jin et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-3c2911b13b5ed6656862e41fe1ef82bbcf97b51d55ec9c3684a233b15b9c29563</citedby><cites>FETCH-LOGICAL-c692t-3c2911b13b5ed6656862e41fe1ef82bbcf97b51d55ec9c3684a233b15b9c29563</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/PMC4121232/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4121232/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79343,79344</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25090005$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Jin, Minfei</creatorcontrib><creatorcontrib>Yang, Zujing</creatorcontrib><creatorcontrib>Ye, Weiping</creatorcontrib><creatorcontrib>Xu, Hongling</creatorcontrib><creatorcontrib>Hua, Xiaolin</creatorcontrib><title>MicroRNA-150 predicts a favorable prognosis in patients with epithelial ovarian cancer, and inhibits cell invasion and metastasis by suppressing transcriptional repressor ZEB1</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>MicroRNA (miR)-150 has been reported to be dramatically downregulated in human epithelial ovarian cancer (EOC) tissues and patients' serum compared to normal controls. This study aimed to investigate clinical significance and molecular mechanisms of miR-150 in EOC. In the current study, quantitative real-time PCR analysis showed that miR-150 was significantly downregulated in human EOC tissues compared to normal tissue samples. Then, we demonstrated the significant associations of miR-150 downregulation with aggressive clinicopathological features of EOC patients, including high clinical stage and pathological grade, and shorter overall and progression-free survivals. More importantly, the multivariate analysis identified miR-150 expression as an independent prognostic biomarker in EOC. After that, luciferase reporter assays demonstrated that Zinc Finger E-Box Binding Homeobox 1 (ZEB1), a crucial regulator of epithelial-to-mesenchymal transition (EMT), was a direct target of miR-150 in EOC cells. Moreover, we found that the ectopic expression of miR-150 could efficiently inhibit cell proliferation, invasion and metastasis by suppressing the expression of ZEB1. Furthermore, we also observed a significantly negative correlation between miR-150 and ZEB1 mRNA expression in EOC tissues (rs = -0.45, P<0.001). In conclusion, these findings offer the convincing evidence that aberrant expression of miR-150 may play a role in tumor progression and prognosis in patients with EOC. Moreover, our data reveal that miR-150 may function as a tumor suppressor and modulate EOC cell proliferation, and invasion by directly and negatively regulating ZEB1, implying the re-expression of miR-150 might be a potential therapeutic strategy for EOC.</description><subject>Binding sites</subject><subject>Biomarkers</subject><subject>Cancer</subject><subject>Cancer metastasis</subject><subject>Cancer therapies</subject><subject>Carcinoma, Ovarian Epithelial</subject><subject>Cell growth</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation</subject><subject>Colorectal cancer</subject><subject>Comparative analysis</subject><subject>Development and progression</subject><subject>Disease Progression</subject><subject>Disease-Free Survival</subject><subject>Down-Regulation</subject><subject>Ectopic expression</subject><subject>Female</subject><subject>Gastric cancer</subject><subject>Gene expression</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Genetic aspects</subject><subject>Gynecology</subject><subject>Health aspects</subject><subject>Homeobox</subject><subject>Homeodomain Proteins - genetics</subject><subject>Homeodomain Proteins - metabolism</subject><subject>Hospitals</subject><subject>Humans</subject><subject>Kaplan-Meier Estimate</subject><subject>Luciferase</subject><subject>Lung cancer</subject><subject>Lymphoma</subject><subject>Medical prognosis</subject><subject>Medical research</subject><subject>Medicine</subject><subject>Medicine and Health Sciences</subject><subject>Mesenchyme</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>MicroRNA</subject><subject>MicroRNAs</subject><subject>MicroRNAs - genetics</subject><subject>MicroRNAs - metabolism</subject><subject>Middle Aged</subject><subject>miRNA</subject><subject>Molecular modelling</subject><subject>Multivariate Analysis</subject><subject>Neoplasm Invasiveness</subject><subject>Neoplasm Metastasis</subject><subject>Neoplasms, Glandular and Epithelial - genetics</subject><subject>Neoplasms, Glandular and Epithelial - pathology</subject><subject>Obstetrics</subject><subject>Ovarian cancer</subject><subject>Ovarian carcinoma</subject><subject>Ovarian Neoplasms - genetics</subject><subject>Ovarian Neoplasms - pathology</subject><subject>Patients</subject><subject>Prognosis</subject><subject>Real-Time Polymerase Chain Reaction</subject><subject>Repressor Proteins - metabolism</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>RNA, Small Interfering - metabolism</subject><subject>Stomach cancer</subject><subject>Tissues</subject><subject>Transcription</subject><subject>Transcription (Genetics)</subject><subject>Transcription Factors - genetics</subject><subject>Transcription Factors - metabolism</subject><subject>Tumor suppressor genes</subject><subject>Womens 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Survival</topic><topic>Down-Regulation</topic><topic>Ectopic expression</topic><topic>Female</topic><topic>Gastric cancer</topic><topic>Gene expression</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Genetic aspects</topic><topic>Gynecology</topic><topic>Health aspects</topic><topic>Homeobox</topic><topic>Homeodomain Proteins - genetics</topic><topic>Homeodomain Proteins - metabolism</topic><topic>Hospitals</topic><topic>Humans</topic><topic>Kaplan-Meier Estimate</topic><topic>Luciferase</topic><topic>Lung cancer</topic><topic>Lymphoma</topic><topic>Medical prognosis</topic><topic>Medical research</topic><topic>Medicine</topic><topic>Medicine and Health Sciences</topic><topic>Mesenchyme</topic><topic>Metastases</topic><topic>Metastasis</topic><topic>MicroRNA</topic><topic>MicroRNAs</topic><topic>MicroRNAs - genetics</topic><topic>MicroRNAs - metabolism</topic><topic>Middle Aged</topic><topic>miRNA</topic><topic>Molecular modelling</topic><topic>Multivariate 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Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jin, Minfei</au><au>Yang, Zujing</au><au>Ye, Weiping</au><au>Xu, Hongling</au><au>Hua, Xiaolin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>MicroRNA-150 predicts a favorable prognosis in patients with epithelial ovarian cancer, and inhibits cell invasion and metastasis by suppressing transcriptional repressor ZEB1</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2014-08-04</date><risdate>2014</risdate><volume>9</volume><issue>8</issue><spage>e103965</spage><epage>e103965</epage><pages>e103965-e103965</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>MicroRNA (miR)-150 has been reported to be dramatically downregulated in human epithelial ovarian cancer (EOC) tissues and patients' serum compared to normal controls. This study aimed to investigate clinical significance and molecular mechanisms of miR-150 in EOC. In the current study, quantitative real-time PCR analysis showed that miR-150 was significantly downregulated in human EOC tissues compared to normal tissue samples. Then, we demonstrated the significant associations of miR-150 downregulation with aggressive clinicopathological features of EOC patients, including high clinical stage and pathological grade, and shorter overall and progression-free survivals. More importantly, the multivariate analysis identified miR-150 expression as an independent prognostic biomarker in EOC. After that, luciferase reporter assays demonstrated that Zinc Finger E-Box Binding Homeobox 1 (ZEB1), a crucial regulator of epithelial-to-mesenchymal transition (EMT), was a direct target of miR-150 in EOC cells. Moreover, we found that the ectopic expression of miR-150 could efficiently inhibit cell proliferation, invasion and metastasis by suppressing the expression of ZEB1. Furthermore, we also observed a significantly negative correlation between miR-150 and ZEB1 mRNA expression in EOC tissues (rs = -0.45, P<0.001). In conclusion, these findings offer the convincing evidence that aberrant expression of miR-150 may play a role in tumor progression and prognosis in patients with EOC. Moreover, our data reveal that miR-150 may function as a tumor suppressor and modulate EOC cell proliferation, and invasion by directly and negatively regulating ZEB1, implying the re-expression of miR-150 might be a potential therapeutic strategy for EOC.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>25090005</pmid><doi>10.1371/journal.pone.0103965</doi><oa>free_for_read</oa></addata></record> |
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| language | eng |
| recordid | cdi_plos_journals_1551148486 |
| source | Public Library of Science (PLoS) Journals Open Access; MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Binding sites Biomarkers Cancer Cancer metastasis Cancer therapies Carcinoma, Ovarian Epithelial Cell growth Cell Line, Tumor Cell Proliferation Colorectal cancer Comparative analysis Development and progression Disease Progression Disease-Free Survival Down-Regulation Ectopic expression Female Gastric cancer Gene expression Gene Expression Regulation, Neoplastic Genetic aspects Gynecology Health aspects Homeobox Homeodomain Proteins - genetics Homeodomain Proteins - metabolism Hospitals Humans Kaplan-Meier Estimate Luciferase Lung cancer Lymphoma Medical prognosis Medical research Medicine Medicine and Health Sciences Mesenchyme Metastases Metastasis MicroRNA MicroRNAs MicroRNAs - genetics MicroRNAs - metabolism Middle Aged miRNA Molecular modelling Multivariate Analysis Neoplasm Invasiveness Neoplasm Metastasis Neoplasms, Glandular and Epithelial - genetics Neoplasms, Glandular and Epithelial - pathology Obstetrics Ovarian cancer Ovarian carcinoma Ovarian Neoplasms - genetics Ovarian Neoplasms - pathology Patients Prognosis Real-Time Polymerase Chain Reaction Repressor Proteins - metabolism Ribonucleic acid RNA RNA, Messenger - genetics RNA, Messenger - metabolism RNA, Small Interfering - metabolism Stomach cancer Tissues Transcription Transcription (Genetics) Transcription Factors - genetics Transcription Factors - metabolism Tumor suppressor genes Womens health Zinc Zinc Finger E-box-Binding Homeobox 1 Zinc finger proteins |
| title | MicroRNA-150 predicts a favorable prognosis in patients with epithelial ovarian cancer, and inhibits cell invasion and metastasis by suppressing transcriptional repressor ZEB1 |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-02T23%3A55%3A48IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=MicroRNA-150%20predicts%20a%20favorable%20prognosis%20in%20patients%20with%20epithelial%20ovarian%20cancer,%20and%20inhibits%20cell%20invasion%20and%20metastasis%20by%20suppressing%20transcriptional%20repressor%20ZEB1&rft.jtitle=PloS%20one&rft.au=Jin,%20Minfei&rft.date=2014-08-04&rft.volume=9&rft.issue=8&rft.spage=e103965&rft.epage=e103965&rft.pages=e103965-e103965&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0103965&rft_dat=%3Cgale_plos_%3EA416975334%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1551148486&rft_id=info:pmid/25090005&rft_galeid=A416975334&rft_doaj_id=oai_doaj_org_article_d10a2b899f704f19aedc0f9002491722&rfr_iscdi=true |