miR-497-5p inhibits cell proliferation and invasion by targeting KCa3.1 in angiosarcoma
Identifieur interne : 008699 ( Ncbi/Merge ); précédent : 008698; suivant : 008700miR-497-5p inhibits cell proliferation and invasion by targeting KCa3.1 in angiosarcoma
Auteurs : Yaobing Chen [République populaire de Chine] ; Dong Kuang [République populaire de Chine] ; Xia Zhao [République populaire de Chine] ; Dong Chen [République populaire de Chine] ; Xiaoyan Wang [République populaire de Chine] ; Qin Yang [République populaire de Chine] ; Jie Wan [République populaire de Chine] ; Yuanli Zhu [République populaire de Chine] ; Yu Wang [République populaire de Chine] ; Shiying Zhang [République populaire de Chine] ; Ying Wang [République populaire de Chine] ; Qiang Tang [République populaire de Chine] ; Mikio Masuzawa [Japon] ; Guoping Wang [République populaire de Chine] ; Yaqi Duan [République populaire de Chine]Source :
- Oncotarget [ 1949-2553 ] ; 2016.
Abstract
Angiosarcoma is a rare malignant mesenchymal tumor with poor prognosis. We aimed to identify malignancy-associated miRNAs and their target genes, and explore biological functions of miRNA and its target in angiosarcoma. By miRNA microarrays and reverse transcription polymerase chain reaction, we identified 1 up-regulated miRNA (miR-222-3p) and 3 down-regulated miRNAs (miR-497-5p, miR-378-3p and miR-483-5p) in human angiosarcomas compared with human capillary hemangiomas. The intermediate-conductance calcium activated potassium channel KCa3.1 was one of the putative target genes of miR-497-5p, and marked up-regulation of KCa3.1 was detected in angiosarcoma biopsy specimens by immunohistochemistry. The inverse correlation of miR-497-5p and KCa3.1 also was observed in the ISO-HAS angiosarcoma cell line at the mRNA and protein levels. The direct targeting of KCa3.1 by miR-497-5p was evidenced by reduced luciferase activity due to complementary binding of miR-497-5p to KCa3.1 mRNA 3′ untranslated region. For the functional role of miR-497-5p/KCa3.1 pair, we showed that application of TRAM-34, a specific KCa3.1 channel blocker, or transfection of ISO-HAS cells with KCa3.1 siRNA or miR-497-5p mimics inhibited cell proliferation, cell cycle progression, and invasion by down-regulating cell-cycle related proteins including cyclin D1, surviving and P53 and down-regulating matrix metallopeptidase 9. In an
Url:
DOI: 10.18632/oncotarget.11252
PubMed: 27531900
PubMed Central: 5295420
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430030</wicri:noRegion></affiliation></author><author><name sortKey="Wang, Xiaoyan" sort="Wang, Xiaoyan" uniqKey="Wang X" first="Xiaoyan" last="Wang">Xiaoyan Wang</name><affiliation wicri:level="1"><nlm:aff id="A1"> Institute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea> Institute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030</wicri:regionArea><wicri:noRegion>Wuhan 430030</wicri:noRegion></affiliation></author><author><name sortKey="Yang, Qin" sort="Yang, Qin" uniqKey="Yang Q" first="Qin" last="Yang">Qin Yang</name><affiliation wicri:level="1"><nlm:aff id="A1"> Institute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea> Institute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030</wicri:regionArea><wicri:noRegion>Wuhan 430030</wicri:noRegion></affiliation></author><author><name sortKey="Wan, Jie" sort="Wan, Jie" uniqKey="Wan J" first="Jie" last="Wan">Jie Wan</name><affiliation wicri:level="1"><nlm:aff id="A1"> Institute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea> Institute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030</wicri:regionArea><wicri:noRegion>Wuhan 430030</wicri:noRegion></affiliation></author><author><name sortKey="Zhu, Yuanli" sort="Zhu, Yuanli" uniqKey="Zhu Y" first="Yuanli" last="Zhu">Yuanli Zhu</name><affiliation wicri:level="1"><nlm:aff id="A1"> Institute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea> Institute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030</wicri:regionArea><wicri:noRegion>Wuhan 430030</wicri:noRegion></affiliation></author><author><name sortKey="Wang, Yu" sort="Wang, Yu" uniqKey="Wang Y" first="Yu" last="Wang">Yu Wang</name><affiliation wicri:level="1"><nlm:aff id="A1"> Institute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea> Institute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030</wicri:regionArea><wicri:noRegion>Wuhan 430030</wicri:noRegion></affiliation></author><author><name sortKey="Zhang, Shiying" sort="Zhang, Shiying" uniqKey="Zhang S" first="Shiying" last="Zhang">Shiying Zhang</name><affiliation wicri:level="1"><nlm:aff id="A2"> Department of Pathology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea> Department of Pathology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030</wicri:regionArea><wicri:noRegion>Wuhan 430030</wicri:noRegion></affiliation></author><author><name sortKey="Wang, Ying" sort="Wang, Ying" uniqKey="Wang Y" first="Ying" last="Wang">Ying Wang</name><affiliation wicri:level="1"><nlm:aff id="A2"> Department of Pathology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China</nlm:aff><country 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first="Mikio" last="Masuzawa">Mikio Masuzawa</name><affiliation wicri:level="1"><nlm:aff id="A4"> Department of Regulation Biochemistry, Kitasato University School of Allied Health Sciences, Minamiku, Sagamihara Kanagawa, 252-0329, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea> Department of Regulation Biochemistry, Kitasato University School of Allied Health Sciences, Minamiku, Sagamihara Kanagawa, 252-0329</wicri:regionArea><wicri:noRegion>252-0329</wicri:noRegion></affiliation></author><author><name sortKey="Wang, Guoping" sort="Wang, Guoping" uniqKey="Wang G" first="Guoping" last="Wang">Guoping Wang</name><affiliation wicri:level="1"><nlm:aff id="A1"> Institute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea> Institute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030</wicri:regionArea><wicri:noRegion>Wuhan 430030</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="A2"> Department of Pathology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea> Department of Pathology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030</wicri:regionArea><wicri:noRegion>Wuhan 430030</wicri:noRegion></affiliation></author><author><name sortKey="Duan, Yaqi" sort="Duan, Yaqi" uniqKey="Duan Y" first="Yaqi" last="Duan">Yaqi Duan</name><affiliation wicri:level="1"><nlm:aff id="A1"> Institute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea> Institute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030</wicri:regionArea><wicri:noRegion>Wuhan 430030</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="A2"> Department of Pathology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea> Department of Pathology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030</wicri:regionArea><wicri:noRegion>Wuhan 430030</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">27531900</idno><idno type="pmc">5295420</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5295420</idno><idno type="RBID">PMC:5295420</idno><idno type="doi">10.18632/oncotarget.11252</idno><date when="2016">2016</date><idno type="wicri:Area/Pmc/Corpus">004269</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">004269</idno><idno type="wicri:Area/Pmc/Curation">004268</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">004268</idno><idno type="wicri:Area/Pmc/Checkpoint">000458</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000458</idno><idno type="wicri:Area/Ncbi/Merge">008699</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">miR-497-5p inhibits cell proliferation and invasion by targeting KCa3.1 in angiosarcoma</title><author><name sortKey="Chen, Yaobing" sort="Chen, Yaobing" uniqKey="Chen Y" first="Yaobing" last="Chen">Yaobing Chen</name><affiliation wicri:level="1"><nlm:aff id="A1"> Institute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea> Institute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030</wicri:regionArea><wicri:noRegion>Wuhan 430030</wicri:noRegion></affiliation></author><author><name sortKey="Kuang, Dong" sort="Kuang, Dong" uniqKey="Kuang D" first="Dong" last="Kuang">Dong Kuang</name><affiliation wicri:level="1"><nlm:aff id="A1"> Institute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea> Institute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030</wicri:regionArea><wicri:noRegion>Wuhan 430030</wicri:noRegion></affiliation></author><author><name sortKey="Zhao, Xia" sort="Zhao, Xia" uniqKey="Zhao X" first="Xia" last="Zhao">Xia Zhao</name><affiliation wicri:level="1"><nlm:aff id="A1"> Institute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea> Institute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030</wicri:regionArea><wicri:noRegion>Wuhan 430030</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="A2"> Department of Pathology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea> Department of Pathology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030</wicri:regionArea><wicri:noRegion>Wuhan 430030</wicri:noRegion></affiliation></author><author><name sortKey="Chen, Dong" sort="Chen, Dong" uniqKey="Chen D" first="Dong" last="Chen">Dong Chen</name><affiliation wicri:level="1"><nlm:aff id="A1"> Institute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea> Institute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030</wicri:regionArea><wicri:noRegion>Wuhan 430030</wicri:noRegion></affiliation></author><author><name sortKey="Wang, Xiaoyan" sort="Wang, Xiaoyan" uniqKey="Wang X" first="Xiaoyan" last="Wang">Xiaoyan Wang</name><affiliation wicri:level="1"><nlm:aff id="A1"> Institute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea> Institute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030</wicri:regionArea><wicri:noRegion>Wuhan 430030</wicri:noRegion></affiliation></author><author><name sortKey="Yang, Qin" sort="Yang, Qin" uniqKey="Yang Q" first="Qin" last="Yang">Qin Yang</name><affiliation wicri:level="1"><nlm:aff id="A1"> Institute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea> Institute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030</wicri:regionArea><wicri:noRegion>Wuhan 430030</wicri:noRegion></affiliation></author><author><name sortKey="Wan, Jie" sort="Wan, Jie" uniqKey="Wan J" first="Jie" last="Wan">Jie Wan</name><affiliation wicri:level="1"><nlm:aff id="A1"> Institute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea> Institute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030</wicri:regionArea><wicri:noRegion>Wuhan 430030</wicri:noRegion></affiliation></author><author><name sortKey="Zhu, Yuanli" sort="Zhu, Yuanli" uniqKey="Zhu Y" first="Yuanli" last="Zhu">Yuanli Zhu</name><affiliation wicri:level="1"><nlm:aff id="A1"> Institute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea> Institute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030</wicri:regionArea><wicri:noRegion>Wuhan 430030</wicri:noRegion></affiliation></author><author><name sortKey="Wang, Yu" sort="Wang, Yu" uniqKey="Wang Y" first="Yu" last="Wang">Yu Wang</name><affiliation wicri:level="1"><nlm:aff id="A1"> Institute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea> Institute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030</wicri:regionArea><wicri:noRegion>Wuhan 430030</wicri:noRegion></affiliation></author><author><name sortKey="Zhang, Shiying" sort="Zhang, Shiying" uniqKey="Zhang S" first="Shiying" last="Zhang">Shiying Zhang</name><affiliation wicri:level="1"><nlm:aff id="A2"> Department of Pathology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea> Department of Pathology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030</wicri:regionArea><wicri:noRegion>Wuhan 430030</wicri:noRegion></affiliation></author><author><name sortKey="Wang, Ying" sort="Wang, Ying" uniqKey="Wang Y" first="Ying" last="Wang">Ying Wang</name><affiliation wicri:level="1"><nlm:aff id="A2"> Department of Pathology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea> Department of Pathology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030</wicri:regionArea><wicri:noRegion>Wuhan 430030</wicri:noRegion></affiliation></author><author><name sortKey="Tang, Qiang" sort="Tang, Qiang" uniqKey="Tang Q" first="Qiang" last="Tang">Qiang Tang</name><affiliation wicri:level="1"><nlm:aff id="A3"> Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea> Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030</wicri:regionArea><wicri:noRegion>Wuhan 430030</wicri:noRegion></affiliation></author><author><name sortKey="Masuzawa, Mikio" sort="Masuzawa, Mikio" uniqKey="Masuzawa M" first="Mikio" last="Masuzawa">Mikio Masuzawa</name><affiliation wicri:level="1"><nlm:aff id="A4"> Department of Regulation Biochemistry, Kitasato University School of Allied Health Sciences, Minamiku, Sagamihara Kanagawa, 252-0329, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea> Department of Regulation Biochemistry, Kitasato University School of Allied Health Sciences, Minamiku, Sagamihara Kanagawa, 252-0329</wicri:regionArea><wicri:noRegion>252-0329</wicri:noRegion></affiliation></author><author><name sortKey="Wang, Guoping" sort="Wang, Guoping" uniqKey="Wang G" first="Guoping" last="Wang">Guoping Wang</name><affiliation wicri:level="1"><nlm:aff id="A1"> Institute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea> Institute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030</wicri:regionArea><wicri:noRegion>Wuhan 430030</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="A2"> Department of Pathology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea> Department of Pathology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030</wicri:regionArea><wicri:noRegion>Wuhan 430030</wicri:noRegion></affiliation></author><author><name sortKey="Duan, Yaqi" sort="Duan, Yaqi" uniqKey="Duan Y" first="Yaqi" last="Duan">Yaqi Duan</name><affiliation wicri:level="1"><nlm:aff id="A1"> Institute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea> Institute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030</wicri:regionArea><wicri:noRegion>Wuhan 430030</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="A2"> Department of Pathology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea> Department of Pathology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030</wicri:regionArea><wicri:noRegion>Wuhan 430030</wicri:noRegion></affiliation></author></analytic><series><title level="j">Oncotarget</title><idno type="eISSN">1949-2553</idno><imprint><date when="2016">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Angiosarcoma is a rare malignant mesenchymal tumor with poor prognosis. We aimed to identify malignancy-associated miRNAs and their target genes, and explore biological functions of miRNA and its target in angiosarcoma. By miRNA microarrays and reverse transcription polymerase chain reaction, we identified 1 up-regulated miRNA (miR-222-3p) and 3 down-regulated miRNAs (miR-497-5p, miR-378-3p and miR-483-5p) in human angiosarcomas compared with human capillary hemangiomas. The intermediate-conductance calcium activated potassium channel KCa3.1 was one of the putative target genes of miR-497-5p, and marked up-regulation of KCa3.1 was detected in angiosarcoma biopsy specimens by immunohistochemistry. The inverse correlation of miR-497-5p and KCa3.1 also was observed in the ISO-HAS angiosarcoma cell line at the mRNA and protein levels. The direct targeting of KCa3.1 by miR-497-5p was evidenced by reduced luciferase activity due to complementary binding of miR-497-5p to KCa3.1 mRNA 3′ untranslated region. For the functional role of miR-497-5p/KCa3.1 pair, we showed that application of TRAM-34, a specific KCa3.1 channel blocker, or transfection of ISO-HAS cells with KCa3.1 siRNA or miR-497-5p mimics inhibited cell proliferation, cell cycle progression, and invasion by down-regulating cell-cycle related proteins including cyclin D1, surviving and P53 and down-regulating matrix metallopeptidase 9. In an <italic>in vivo</italic> angiosarcoma xenograft model, TRAM-34 or miR-497-5p mimics both inhibited tumor growth. In conclusion, the tumor suppressor miR-497-5p down-regulates KCa3.1 expression and contributes to the inhibition of angiosarcoma malignancy development. 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Oncotarget</journal-id><journal-id journal-id-type="iso-abbrev">Oncotarget</journal-id><journal-id journal-id-type="publisher-id">Oncotarget</journal-id><journal-id journal-id-type="publisher-id">ImpactJ</journal-id><journal-title-group><journal-title>Oncotarget</journal-title></journal-title-group><issn pub-type="epub">1949-2553</issn><publisher><publisher-name>Impact Journals LLC</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">27531900</article-id><article-id pub-id-type="pmc">5295420</article-id><article-id pub-id-type="publisher-id">11252</article-id><article-id pub-id-type="doi">10.18632/oncotarget.11252</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Paper</subject></subj-group></article-categories><title-group><article-title>miR-497-5p inhibits cell proliferation and invasion by targeting KCa3.1 in angiosarcoma</article-title></title-group><contrib-group><contrib contrib-type="author" equal-contrib="yes"><name><surname>Chen</surname><given-names>Yaobing</given-names></name><xref ref-type="aff" rid="A1"><sup>1</sup></xref></contrib><contrib contrib-type="author" equal-contrib="yes"><name><surname>Kuang</surname><given-names>Dong</given-names></name><xref ref-type="aff" rid="A1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Zhao</surname><given-names>Xia</given-names></name><xref ref-type="aff" rid="A1"><sup>1</sup></xref><xref ref-type="aff" rid="A2"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Chen</surname><given-names>Dong</given-names></name><xref ref-type="aff" rid="A1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Wang</surname><given-names>Xiaoyan</given-names></name><xref ref-type="aff" rid="A1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Yang</surname><given-names>Qin</given-names></name><xref ref-type="aff" rid="A1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Wan</surname><given-names>Jie</given-names></name><xref ref-type="aff" rid="A1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Zhu</surname><given-names>Yuanli</given-names></name><xref ref-type="aff" rid="A1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Wang</surname><given-names>Yu</given-names></name><xref ref-type="aff" rid="A1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Zhang</surname><given-names>Shiying</given-names></name><xref ref-type="aff" rid="A2"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Wang</surname><given-names>Ying</given-names></name><xref ref-type="aff" rid="A2"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Tang</surname><given-names>Qiang</given-names></name><xref ref-type="aff" rid="A3"><sup>3</sup></xref></contrib><contrib contrib-type="author"><name><surname>Masuzawa</surname><given-names>Mikio</given-names></name><xref ref-type="aff" rid="A4"><sup>4</sup></xref></contrib><contrib contrib-type="author"><name><surname>Wang</surname><given-names>Guoping</given-names></name><xref ref-type="aff" rid="A1"><sup>1</sup></xref><xref ref-type="aff" rid="A2"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Duan</surname><given-names>Yaqi</given-names></name><xref ref-type="aff" rid="A1"><sup>1</sup></xref><xref ref-type="aff" rid="A2"><sup>2</sup></xref></contrib></contrib-group><aff id="A1"><sup>1</sup> Institute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China</aff><aff id="A2"><sup>2</sup> Department of Pathology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China</aff><aff id="A3"><sup>3</sup> Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China</aff><aff id="A4"><sup>4</sup> Department of Regulation Biochemistry, Kitasato University School of Allied Health Sciences, Minamiku, Sagamihara Kanagawa, 252-0329, Japan</aff><author-notes><corresp id="cor1"><bold>Correspondence to:</bold> Guoping Wang, <email>wanggp@hust.edu.cn</email></corresp><corresp id="cor2">Yaqi Duan, <email>yqduan@hust.edu.cn</email></corresp></author-notes><pub-date pub-type="collection"><day>6</day><month>9</month><year>2016</year></pub-date><pub-date pub-type="epub"><day>12</day><month>8</month><year>2016</year></pub-date><volume>7</volume><issue>36</issue><fpage>58148</fpage><lpage>58161</lpage><history><date date-type="received"><day>28</day><month>10</month><year>2015</year></date><date date-type="accepted"><day>26</day><month>7</month><year>2016</year></date></history><permissions><copyright-statement>Copyright: © 2016 Chen et al.</copyright-statement><copyright-year>2016</copyright-year><license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by/2.5/"><license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</license-p></license></permissions><abstract><p>Angiosarcoma is a rare malignant mesenchymal tumor with poor prognosis. We aimed to identify malignancy-associated miRNAs and their target genes, and explore biological functions of miRNA and its target in angiosarcoma. By miRNA microarrays and reverse transcription polymerase chain reaction, we identified 1 up-regulated miRNA (miR-222-3p) and 3 down-regulated miRNAs (miR-497-5p, miR-378-3p and miR-483-5p) in human angiosarcomas compared with human capillary hemangiomas. The intermediate-conductance calcium activated potassium channel KCa3.1 was one of the putative target genes of miR-497-5p, and marked up-regulation of KCa3.1 was detected in angiosarcoma biopsy specimens by immunohistochemistry. The inverse correlation of miR-497-5p and KCa3.1 also was observed in the ISO-HAS angiosarcoma cell line at the mRNA and protein levels. The direct targeting of KCa3.1 by miR-497-5p was evidenced by reduced luciferase activity due to complementary binding of miR-497-5p to KCa3.1 mRNA 3′ untranslated region. For the functional role of miR-497-5p/KCa3.1 pair, we showed that application of TRAM-34, a specific KCa3.1 channel blocker, or transfection of ISO-HAS cells with KCa3.1 siRNA or miR-497-5p mimics inhibited cell proliferation, cell cycle progression, and invasion by down-regulating cell-cycle related proteins including cyclin D1, surviving and P53 and down-regulating matrix metallopeptidase 9. In an <italic>in vivo</italic> angiosarcoma xenograft model, TRAM-34 or miR-497-5p mimics both inhibited tumor growth. In conclusion, the tumor suppressor miR-497-5p down-regulates KCa3.1 expression and contributes to the inhibition of angiosarcoma malignancy development. The miR-497-5p or KCa3.1 might be potential new targets for angiosarcoma treatment.</p></abstract><kwd-group><kwd>sarcoma</kwd><kwd>cell cycle</kwd><kwd>potassium channel</kwd><kwd>hemangioma</kwd></kwd-group></article-meta></front></pmc><affiliations><list><country><li>Japon</li><li>République populaire de Chine</li></country></list><tree><country name="République populaire de Chine"><noRegion><name sortKey="Chen, Yaobing" sort="Chen, Yaobing" uniqKey="Chen Y" first="Yaobing" last="Chen">Yaobing Chen</name></noRegion><name sortKey="Chen, Dong" sort="Chen, Dong" uniqKey="Chen D" first="Dong" last="Chen">Dong Chen</name><name sortKey="Duan, Yaqi" sort="Duan, Yaqi" uniqKey="Duan Y" first="Yaqi" last="Duan">Yaqi Duan</name><name sortKey="Duan, Yaqi" sort="Duan, Yaqi" uniqKey="Duan Y" first="Yaqi" last="Duan">Yaqi Duan</name><name sortKey="Kuang, Dong" sort="Kuang, Dong" uniqKey="Kuang D" first="Dong" last="Kuang">Dong Kuang</name><name sortKey="Tang, Qiang" sort="Tang, Qiang" uniqKey="Tang Q" first="Qiang" last="Tang">Qiang Tang</name><name sortKey="Wan, Jie" sort="Wan, Jie" uniqKey="Wan J" first="Jie" last="Wan">Jie Wan</name><name sortKey="Wang, Guoping" sort="Wang, Guoping" uniqKey="Wang G" first="Guoping" last="Wang">Guoping Wang</name><name sortKey="Wang, Guoping" sort="Wang, Guoping" uniqKey="Wang G" first="Guoping" last="Wang">Guoping Wang</name><name sortKey="Wang, Xiaoyan" sort="Wang, Xiaoyan" uniqKey="Wang X" first="Xiaoyan" last="Wang">Xiaoyan Wang</name><name sortKey="Wang, Ying" sort="Wang, Ying" uniqKey="Wang Y" first="Ying" last="Wang">Ying Wang</name><name sortKey="Wang, Yu" sort="Wang, Yu" uniqKey="Wang Y" first="Yu" last="Wang">Yu Wang</name><name sortKey="Yang, Qin" sort="Yang, Qin" uniqKey="Yang Q" first="Qin" last="Yang">Qin Yang</name><name sortKey="Zhang, Shiying" sort="Zhang, Shiying" uniqKey="Zhang S" first="Shiying" last="Zhang">Shiying Zhang</name><name sortKey="Zhao, Xia" sort="Zhao, Xia" uniqKey="Zhao X" first="Xia" last="Zhao">Xia Zhao</name><name sortKey="Zhao, Xia" sort="Zhao, Xia" uniqKey="Zhao X" first="Xia" last="Zhao">Xia Zhao</name><name sortKey="Zhu, Yuanli" sort="Zhu, Yuanli" uniqKey="Zhu Y" first="Yuanli" last="Zhu">Yuanli Zhu</name></country><country name="Japon"><noRegion><name sortKey="Masuzawa, Mikio" sort="Masuzawa, Mikio" uniqKey="Masuzawa M" first="Mikio" last="Masuzawa">Mikio Masuzawa</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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