The histone methyltransferase WHSC1 is regulated by EZH2 and is important for ovarian clear cell carcinoma cell proliferation
Identifieur interne : 000347 ( Main/Exploration ); précédent : 000346; suivant : 000348The histone methyltransferase WHSC1 is regulated by EZH2 and is important for ovarian clear cell carcinoma cell proliferation
Auteurs : Machiko Kojima [Japon] ; Kenbun Sone [Japon] ; Katsutoshi Oda [Japon] ; Ryuji Hamamoto [Japon] ; Syuzo Kaneko [Japon] ; Shinya Oki [Japon] ; Asako Kukita [Japon] ; Hidenori Machino [Japon] ; Harunori Honjoh [Japon] ; Yoshiko Kawata [Japon] ; Tomoko Kashiyama [Japon] ; Kayo Asada [Japon] ; Michihiro Tanikawa [Japon] ; Mayuyo Mori-Uchino [Japon] ; Tetsushi Tsuruga [Japon] ; Kazunori Nagasaka [Japon] ; Yoko Matsumoto [Japon] ; Osamu Wada-Hiraike [Japon] ; Yutaka Osuga [Japon] ; Tomoyuki Fujii [Japon]Source :
- BMC Cancer [ 1471-2407 ] ; 2019.
Abstract
Wolf-Hirschhorn syndrome candidate gene-1 (WHSC1), a histone methyltransferase, has been found to be upregulated and its expression to be correlated with expression of enhancer of zeste homolog 2 (EZH2) in several cancers. In this study, we evaluated the role of WHSC1 and its therapeutic significance in ovarian clear cell carcinoma (OCCC).
First, we analyzed
Both quantitative PCR and immunohistochemical analysis revealed that
WHSC1 overexpression induced cell growth and its expression is, at least in part, regulated by EZH2. Further functional analysis will reveal whether WHSC1 is a promising therapeutic target for OCCC.
The online version of this article (10.1186/s12885-019-5638-9) contains supplementary material, which is available to authorized users.
Url:
DOI: 10.1186/s12885-019-5638-9
PubMed: 31092221
PubMed Central: 6521555
Affiliations:
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Gynecology,</institution><institution>Teikyo University School of Medicine,</institution></institution-wrap>2-11-1, Kaga, Itabashi-ku, Tokyo, 173 0003 Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>2-11-1, Kaga, Itabashi-ku, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author><author><name sortKey="Matsumoto, Yoko" sort="Matsumoto, Yoko" uniqKey="Matsumoto Y" first="Yoko" last="Matsumoto">Yoko Matsumoto</name><affiliation wicri:level="3"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2151 536X</institution-id><institution-id institution-id-type="GRID">grid.26999.3d</institution-id><institution>Department of Obstetrics and Gynecology,</institution><institution>Graduate School of Medicine, The University of Tokyo,</institution></institution-wrap>7-3-1 Hongo Bunkyo-ku, Tokyo, 113-8655 Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>7-3-1 Hongo Bunkyo-ku, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author><author><name sortKey="Wada Hiraike, Osamu" sort="Wada Hiraike, Osamu" uniqKey="Wada Hiraike O" first="Osamu" last="Wada-Hiraike">Osamu Wada-Hiraike</name><affiliation wicri:level="3"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2151 536X</institution-id><institution-id institution-id-type="GRID">grid.26999.3d</institution-id><institution>Department of Obstetrics and Gynecology,</institution><institution>Graduate School of Medicine, The University of Tokyo,</institution></institution-wrap>7-3-1 Hongo Bunkyo-ku, Tokyo, 113-8655 Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>7-3-1 Hongo Bunkyo-ku, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author><author><name sortKey="Osuga, Yutaka" sort="Osuga, Yutaka" uniqKey="Osuga Y" first="Yutaka" last="Osuga">Yutaka Osuga</name><affiliation wicri:level="3"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2151 536X</institution-id><institution-id institution-id-type="GRID">grid.26999.3d</institution-id><institution>Department of Obstetrics and Gynecology,</institution><institution>Graduate School of Medicine, The University of Tokyo,</institution></institution-wrap>7-3-1 Hongo Bunkyo-ku, Tokyo, 113-8655 Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>7-3-1 Hongo Bunkyo-ku, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author><author><name sortKey="Fujii, Tomoyuki" sort="Fujii, Tomoyuki" uniqKey="Fujii T" first="Tomoyuki" last="Fujii">Tomoyuki 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sortKey="Kojima, Machiko" sort="Kojima, Machiko" uniqKey="Kojima M" first="Machiko" last="Kojima">Machiko Kojima</name><affiliation wicri:level="3"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2151 536X</institution-id><institution-id institution-id-type="GRID">grid.26999.3d</institution-id><institution>Department of Obstetrics and Gynecology,</institution><institution>Graduate School of Medicine, The University of Tokyo,</institution></institution-wrap>7-3-1 Hongo Bunkyo-ku, Tokyo, 113-8655 Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>7-3-1 Hongo Bunkyo-ku, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author><author><name sortKey="Sone, Kenbun" sort="Sone, Kenbun" uniqKey="Sone K" first="Kenbun" last="Sone">Kenbun Sone</name><affiliation wicri:level="3"><nlm:aff id="Aff1"><institution-wrap><institution-id 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Gynecology,</institution><institution>Graduate School of Medicine, The University of Tokyo,</institution></institution-wrap>7-3-1 Hongo Bunkyo-ku, Tokyo, 113-8655 Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>7-3-1 Hongo Bunkyo-ku, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author><author><name sortKey="Hamamoto, Ryuji" sort="Hamamoto, Ryuji" uniqKey="Hamamoto R" first="Ryuji" last="Hamamoto">Ryuji Hamamoto</name><affiliation wicri:level="3"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2168 5385</institution-id><institution-id institution-id-type="GRID">grid.272242.3</institution-id><institution>Division of Molecular Modification and Cancer Biology,</institution><institution>National Cancer Center Research Institute,</institution></institution-wrap>5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045 Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>5-1-1 Tsukiji, Chuo-ku, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author><author><name sortKey="Kaneko, Syuzo" sort="Kaneko, Syuzo" uniqKey="Kaneko S" first="Syuzo" last="Kaneko">Syuzo Kaneko</name><affiliation wicri:level="3"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2168 5385</institution-id><institution-id institution-id-type="GRID">grid.272242.3</institution-id><institution>Division of Molecular Modification and Cancer Biology,</institution><institution>National Cancer Center Research Institute,</institution></institution-wrap>5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045 Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>5-1-1 Tsukiji, Chuo-ku, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author><author><name sortKey="Oki, Shinya" sort="Oki, Shinya" uniqKey="Oki S" first="Shinya" last="Oki">Shinya Oki</name><affiliation wicri:level="3"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2151 536X</institution-id><institution-id institution-id-type="GRID">grid.26999.3d</institution-id><institution>Department of Obstetrics and Gynecology,</institution><institution>Graduate School of Medicine, The University of Tokyo,</institution></institution-wrap>7-3-1 Hongo Bunkyo-ku, Tokyo, 113-8655 Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>7-3-1 Hongo Bunkyo-ku, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author><author><name sortKey="Kukita, Asako" sort="Kukita, Asako" uniqKey="Kukita A" first="Asako" last="Kukita">Asako Kukita</name><affiliation wicri:level="3"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2151 536X</institution-id><institution-id institution-id-type="GRID">grid.26999.3d</institution-id><institution>Department of Obstetrics and Gynecology,</institution><institution>Graduate School of Medicine, The University of Tokyo,</institution></institution-wrap>7-3-1 Hongo Bunkyo-ku, Tokyo, 113-8655 Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>7-3-1 Hongo Bunkyo-ku, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author><author><name sortKey="Machino, Hidenori" sort="Machino, Hidenori" uniqKey="Machino H" first="Hidenori" last="Machino">Hidenori Machino</name><affiliation wicri:level="3"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2151 536X</institution-id><institution-id institution-id-type="GRID">grid.26999.3d</institution-id><institution>Department of Obstetrics and Gynecology,</institution><institution>Graduate School of Medicine, The University of Tokyo,</institution></institution-wrap>7-3-1 Hongo Bunkyo-ku, Tokyo, 113-8655 Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>7-3-1 Hongo Bunkyo-ku, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author><author><name sortKey="Honjoh, Harunori" sort="Honjoh, Harunori" uniqKey="Honjoh H" first="Harunori" last="Honjoh">Harunori Honjoh</name><affiliation wicri:level="3"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2151 536X</institution-id><institution-id institution-id-type="GRID">grid.26999.3d</institution-id><institution>Department of Obstetrics and Gynecology,</institution><institution>Graduate School of Medicine, The University of Tokyo,</institution></institution-wrap>7-3-1 Hongo Bunkyo-ku, Tokyo, 113-8655 Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>7-3-1 Hongo Bunkyo-ku, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author><author><name sortKey="Kawata, Yoshiko" sort="Kawata, Yoshiko" uniqKey="Kawata Y" first="Yoshiko" last="Kawata">Yoshiko Kawata</name><affiliation wicri:level="3"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2151 536X</institution-id><institution-id institution-id-type="GRID">grid.26999.3d</institution-id><institution>Department of Obstetrics and Gynecology,</institution><institution>Graduate School of Medicine, The University of Tokyo,</institution></institution-wrap>7-3-1 Hongo Bunkyo-ku, Tokyo, 113-8655 Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>7-3-1 Hongo Bunkyo-ku, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author><author><name sortKey="Kashiyama, Tomoko" sort="Kashiyama, Tomoko" uniqKey="Kashiyama T" first="Tomoko" last="Kashiyama">Tomoko Kashiyama</name><affiliation wicri:level="3"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2151 536X</institution-id><institution-id institution-id-type="GRID">grid.26999.3d</institution-id><institution>Department of Obstetrics and Gynecology,</institution><institution>Graduate School of Medicine, The University of Tokyo,</institution></institution-wrap>7-3-1 Hongo Bunkyo-ku, Tokyo, 113-8655 Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>7-3-1 Hongo Bunkyo-ku, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author><author><name sortKey="Asada, Kayo" sort="Asada, Kayo" uniqKey="Asada K" first="Kayo" last="Asada">Kayo Asada</name><affiliation wicri:level="3"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2151 536X</institution-id><institution-id institution-id-type="GRID">grid.26999.3d</institution-id><institution>Department of Obstetrics and Gynecology,</institution><institution>Graduate School of Medicine, The University of Tokyo,</institution></institution-wrap>7-3-1 Hongo Bunkyo-ku, Tokyo, 113-8655 Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>7-3-1 Hongo Bunkyo-ku, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author><author><name sortKey="Tanikawa, Michihiro" sort="Tanikawa, Michihiro" uniqKey="Tanikawa M" first="Michihiro" last="Tanikawa">Michihiro Tanikawa</name><affiliation wicri:level="3"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2151 536X</institution-id><institution-id institution-id-type="GRID">grid.26999.3d</institution-id><institution>Department of Obstetrics and Gynecology,</institution><institution>Graduate School of Medicine, The University of Tokyo,</institution></institution-wrap>7-3-1 Hongo Bunkyo-ku, Tokyo, 113-8655 Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>7-3-1 Hongo Bunkyo-ku, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author><author><name sortKey="Mori Uchino, Mayuyo" sort="Mori Uchino, Mayuyo" uniqKey="Mori Uchino M" first="Mayuyo" last="Mori-Uchino">Mayuyo Mori-Uchino</name><affiliation wicri:level="3"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2151 536X</institution-id><institution-id institution-id-type="GRID">grid.26999.3d</institution-id><institution>Department of Obstetrics and Gynecology,</institution><institution>Graduate School of Medicine, The University of Tokyo,</institution></institution-wrap>7-3-1 Hongo Bunkyo-ku, Tokyo, 113-8655 Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>7-3-1 Hongo Bunkyo-ku, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author><author><name sortKey="Tsuruga, Tetsushi" sort="Tsuruga, Tetsushi" uniqKey="Tsuruga T" first="Tetsushi" last="Tsuruga">Tetsushi Tsuruga</name><affiliation wicri:level="3"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2151 536X</institution-id><institution-id institution-id-type="GRID">grid.26999.3d</institution-id><institution>Department of Obstetrics and Gynecology,</institution><institution>Graduate School of Medicine, The University of Tokyo,</institution></institution-wrap>7-3-1 Hongo Bunkyo-ku, Tokyo, 113-8655 Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>7-3-1 Hongo Bunkyo-ku, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author><author><name sortKey="Nagasaka, Kazunori" sort="Nagasaka, Kazunori" uniqKey="Nagasaka K" first="Kazunori" last="Nagasaka">Kazunori Nagasaka</name><affiliation wicri:level="3"><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="ISNI">0000 0000 9239 9995</institution-id><institution-id institution-id-type="GRID">grid.264706.1</institution-id><institution>Department of Obstetrics and Gynecology,</institution><institution>Teikyo University School of Medicine,</institution></institution-wrap>2-11-1, Kaga, Itabashi-ku, Tokyo, 173 0003 Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>2-11-1, Kaga, Itabashi-ku, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author><author><name sortKey="Matsumoto, Yoko" sort="Matsumoto, Yoko" uniqKey="Matsumoto Y" first="Yoko" last="Matsumoto">Yoko Matsumoto</name><affiliation wicri:level="3"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2151 536X</institution-id><institution-id institution-id-type="GRID">grid.26999.3d</institution-id><institution>Department of Obstetrics and Gynecology,</institution><institution>Graduate School of Medicine, The University of Tokyo,</institution></institution-wrap>7-3-1 Hongo Bunkyo-ku, Tokyo, 113-8655 Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>7-3-1 Hongo Bunkyo-ku, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author><author><name sortKey="Wada Hiraike, Osamu" sort="Wada Hiraike, Osamu" uniqKey="Wada Hiraike O" first="Osamu" last="Wada-Hiraike">Osamu Wada-Hiraike</name><affiliation wicri:level="3"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2151 536X</institution-id><institution-id institution-id-type="GRID">grid.26999.3d</institution-id><institution>Department of Obstetrics and Gynecology,</institution><institution>Graduate School of Medicine, The University of Tokyo,</institution></institution-wrap>7-3-1 Hongo Bunkyo-ku, Tokyo, 113-8655 Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>7-3-1 Hongo Bunkyo-ku, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author><author><name sortKey="Osuga, Yutaka" sort="Osuga, Yutaka" uniqKey="Osuga Y" first="Yutaka" last="Osuga">Yutaka Osuga</name><affiliation wicri:level="3"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2151 536X</institution-id><institution-id institution-id-type="GRID">grid.26999.3d</institution-id><institution>Department of Obstetrics and Gynecology,</institution><institution>Graduate School of Medicine, The University of Tokyo,</institution></institution-wrap>7-3-1 Hongo Bunkyo-ku, Tokyo, 113-8655 Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>7-3-1 Hongo Bunkyo-ku, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author><author><name sortKey="Fujii, Tomoyuki" sort="Fujii, Tomoyuki" uniqKey="Fujii T" first="Tomoyuki" last="Fujii">Tomoyuki Fujii</name><affiliation wicri:level="3"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2151 536X</institution-id><institution-id institution-id-type="GRID">grid.26999.3d</institution-id><institution>Department of Obstetrics and Gynecology,</institution><institution>Graduate School of Medicine, The University of Tokyo,</institution></institution-wrap>7-3-1 Hongo Bunkyo-ku, Tokyo, 113-8655 Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>7-3-1 Hongo Bunkyo-ku, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author></analytic><series><title level="j">BMC Cancer</title><idno type="eISSN">1471-2407</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Background</title><p id="Par1">Wolf-Hirschhorn syndrome candidate gene-1 (WHSC1), a histone methyltransferase, has been found to be upregulated and its expression to be correlated with expression of enhancer of zeste homolog 2 (EZH2) in several cancers. In this study, we evaluated the role of WHSC1 and its therapeutic significance in ovarian clear cell carcinoma (OCCC).</p></sec><sec><title>Methods</title><p id="Par2">First, we analyzed <italic>WHSC1</italic> expression by quantitative PCR and immunohistochemistry using 23 clinical OCCC specimens. Second, the involvement of WHSC1 in OCCC cell proliferation was evaluated by MTT assays after siRNA-mediated WHSC1 knockdown. We also performed flow cytometry (FACS) to address the effect of WHSC1 on cell cycle. To examine the functional relationship between EZH2 and WHSC1, we knocked down EZH2 using siRNAs and checked the expression levels of WHSC1 and its histone mark H3K36m2 in OCCC cell lines. Finally, we checked <italic>WHSC1</italic> expression after treatment with the selective inhibitor, GSK126.</p></sec><sec><title>Results</title><p id="Par3">Both quantitative PCR and immunohistochemical analysis revealed that <italic>WHSC1</italic> was significantly overexpressed in OCCC tissues compared with that in normal ovarian tissues. MTT assay revealed that knockdown of WHSC1 suppressed cell proliferation, and H3K36me2 levels were found to be decreased in immunoblotting. FACS revealed that WHSC1 knockdown affected the cell cycle. We also confirmed that WHSC1 expression was suppressed by EZH2 knockdown or inhibition, indicating that EZH2 is upstream of WHSC1 in OCCC cells<italic>.</italic></p></sec><sec><title>Conclusions</title><p id="Par4">WHSC1 overexpression induced cell growth and its expression is, at least in part, regulated by EZH2. Further functional analysis will reveal whether WHSC1 is a promising therapeutic target for OCCC.</p></sec><sec><title>Electronic supplementary material</title><p>The online version of this article (10.1186/s12885-019-5638-9) contains supplementary material, which is available to authorized users.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Takano, M" uniqKey="Takano M">M Takano</name></author><author><name sortKey="Sugiyama, T" uniqKey="Sugiyama T">T Sugiyama</name></author><author><name sortKey="Yaegashi, N" uniqKey="Yaegashi N">N Yaegashi</name></author><author><name sortKey="Sakuma, M" uniqKey="Sakuma M">M Sakuma</name></author><author><name sortKey="Suzuki, M" uniqKey="Suzuki M">M Suzuki</name></author><author><name sortKey="Saga, Y" uniqKey="Saga Y">Y Saga</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jones, S" uniqKey="Jones 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S" uniqKey="Cho H">H-S Cho</name></author><author><name sortKey="Kiyotani, K" uniqKey="Kiyotani K">K Kiyotani</name></author><author><name sortKey="Alachkar, H" uniqKey="Alachkar H">H Alachkar</name></author><author><name sortKey="Zuo, Z" uniqKey="Zuo Z">Z Zuo</name></author><author><name sortKey="Nakakido, M" uniqKey="Nakakido M">M Nakakido</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Evans, Dl" uniqKey="Evans D">DL Evans</name></author><author><name sortKey="Zhang, H" uniqKey="Zhang H">H Zhang</name></author><author><name sortKey="Ham, H" uniqKey="Ham H">H Ham</name></author><author><name sortKey="Pei, H" uniqKey="Pei H">H Pei</name></author><author><name sortKey="Lee, Sb" uniqKey="Lee S">SB Lee</name></author><author><name sortKey="Kim, Jj" uniqKey="Kim J">JJ Kim</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Knutson, Sk" uniqKey="Knutson S">SK Knutson</name></author><author><name sortKey="Wigle, Tj" uniqKey="Wigle T">TJ Wigle</name></author><author><name sortKey="Warholic, Nm" uniqKey="Warholic N">NM Warholic</name></author><author><name sortKey="Sneeringer, Cj" uniqKey="Sneeringer C">CJ Sneeringer</name></author><author><name sortKey="Allain, Cj" uniqKey="Allain C">CJ Allain</name></author><author><name sortKey="Klaus, Cr" uniqKey="Klaus C">CR Klaus</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Mccabe, Mt" uniqKey="Mccabe M">MT McCabe</name></author><author><name sortKey="Ott, Hm" uniqKey="Ott H">HM Ott</name></author><author><name sortKey="Ganji, G" uniqKey="Ganji G">G Ganji</name></author><author><name sortKey="Korenchuk, S" uniqKey="Korenchuk S">S Korenchuk</name></author><author><name sortKey="Thompson, C" uniqKey="Thompson C">C Thompson</name></author><author><name sortKey="Van Aller, Gs" uniqKey="Van Aller G">GS Van Aller</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Asangani, Ia" uniqKey="Asangani I">IA Asangani</name></author><author><name sortKey="Ateeq, B" uniqKey="Ateeq B">B Ateeq</name></author><author><name sortKey="Cao, Q" uniqKey="Cao Q">Q Cao</name></author><author><name sortKey="Dodson, L" uniqKey="Dodson L">L Dodson</name></author><author><name sortKey="Pandhi, M" uniqKey="Pandhi M">M Pandhi</name></author><author><name sortKey="Kunju, Lp" uniqKey="Kunju L">LP Kunju</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Japon</li></country><region><li>Région de Kantō</li></region><settlement><li>Tokyo</li></settlement></list><tree><country name="Japon"><region name="Région de Kantō"><name sortKey="Kojima, Machiko" sort="Kojima, Machiko" uniqKey="Kojima M" first="Machiko" last="Kojima">Machiko Kojima</name></region><name sortKey="Asada, Kayo" sort="Asada, Kayo" uniqKey="Asada K" first="Kayo" last="Asada">Kayo Asada</name><name sortKey="Fujii, Tomoyuki" sort="Fujii, Tomoyuki" uniqKey="Fujii T" first="Tomoyuki" last="Fujii">Tomoyuki Fujii</name><name sortKey="Hamamoto, Ryuji" sort="Hamamoto, Ryuji" uniqKey="Hamamoto R" first="Ryuji" last="Hamamoto">Ryuji Hamamoto</name><name sortKey="Honjoh, Harunori" sort="Honjoh, Harunori" uniqKey="Honjoh H" first="Harunori" last="Honjoh">Harunori Honjoh</name><name sortKey="Kaneko, Syuzo" sort="Kaneko, Syuzo" uniqKey="Kaneko S" first="Syuzo" last="Kaneko">Syuzo Kaneko</name><name sortKey="Kashiyama, Tomoko" sort="Kashiyama, Tomoko" uniqKey="Kashiyama T" first="Tomoko" last="Kashiyama">Tomoko Kashiyama</name><name sortKey="Kawata, Yoshiko" sort="Kawata, Yoshiko" uniqKey="Kawata Y" first="Yoshiko" last="Kawata">Yoshiko Kawata</name><name sortKey="Kukita, Asako" sort="Kukita, Asako" uniqKey="Kukita A" first="Asako" last="Kukita">Asako Kukita</name><name sortKey="Machino, Hidenori" sort="Machino, Hidenori" uniqKey="Machino H" first="Hidenori" last="Machino">Hidenori Machino</name><name sortKey="Matsumoto, Yoko" sort="Matsumoto, Yoko" uniqKey="Matsumoto Y" first="Yoko" last="Matsumoto">Yoko Matsumoto</name><name sortKey="Mori Uchino, Mayuyo" sort="Mori Uchino, Mayuyo" uniqKey="Mori Uchino M" first="Mayuyo" last="Mori-Uchino">Mayuyo Mori-Uchino</name><name sortKey="Nagasaka, Kazunori" sort="Nagasaka, Kazunori" uniqKey="Nagasaka K" first="Kazunori" last="Nagasaka">Kazunori Nagasaka</name><name sortKey="Oda, Katsutoshi" sort="Oda, Katsutoshi" uniqKey="Oda K" first="Katsutoshi" last="Oda">Katsutoshi Oda</name><name sortKey="Oki, Shinya" sort="Oki, Shinya" uniqKey="Oki S" first="Shinya" last="Oki">Shinya Oki</name><name sortKey="Osuga, Yutaka" sort="Osuga, Yutaka" uniqKey="Osuga Y" first="Yutaka" last="Osuga">Yutaka Osuga</name><name sortKey="Sone, Kenbun" sort="Sone, Kenbun" uniqKey="Sone K" first="Kenbun" last="Sone">Kenbun Sone</name><name sortKey="Tanikawa, Michihiro" sort="Tanikawa, Michihiro" uniqKey="Tanikawa M" first="Michihiro" last="Tanikawa">Michihiro Tanikawa</name><name sortKey="Tsuruga, Tetsushi" sort="Tsuruga, Tetsushi" uniqKey="Tsuruga T" first="Tetsushi" last="Tsuruga">Tetsushi Tsuruga</name><name sortKey="Wada Hiraike, Osamu" sort="Wada Hiraike, Osamu" uniqKey="Wada Hiraike O" first="Osamu" last="Wada-Hiraike">Osamu Wada-Hiraike</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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