國家衛生研究院 NHRI:Item 3990099045/10536
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    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/10536


    Title: Epigenetic regulation of NOTCH1 and NOTCH3 by KMT2A inhibits glioma proliferation
    Authors: Huang, YC;Lin, SJ;Shih, HY;Chou, CH;Chu, HH;Chiu, CC;Yuh, CH;Yeh, TH;Cheng, YC
    Contributors: Institute of Molecular and Genomic Medicine
    Abstract: Glioblastomas are among the most fatal brain tumors; however, the molecular determinants of their tumorigenic behavior are not adequately defined. In this study, we analyzed the role of KMT2A in the glioblastoma cell line U-87 MG. KMT2A knockdown promoted cell proliferation. Moreover, it increased the DNA methylation of NOTCH1 and NOTCH3 and reduced the expression of NOTCH1 and NOTCH3. NOTCH1 or NOTCH3 activation inhibited U-87 MG cell proliferation, whereas NOTCH1 and NOTCH3 inhibition by shRNAs induced cell proliferation, thus demonstrating the tumor-suppressive ability of NOTCH1 and NOTCH3 in U-87 MG cells. The induced cell proliferation caused by KMT2A knockdown could be nullified by using either constitutively active NOTCH1 or constitutively active NOTCH3. This result demonstrates that KMT2A positively regulates NOTCH1 and NOTCH3 and that this mechanism is essential for inhibiting the U-87 MG cell proliferation. The role of KMT2A knockdown in promoting tumor growth was further confirmed in vivo by transplanting U-87 MG cells into the brains of zebrafish larvae. In conclusion, we identified KMT2A-NOTCH as a negative regulatory cascade for glioblastoma cell proliferation, and this result provides important information for KMT2A- or NOTCH-targeted therapeutic strategies for brain tumors.
    Date: 2017-09
    Relation: Oncotarget. 2017 Aug;8(38):63110-63120.
    Link to: http://dx.doi.org/10.18632/oncotarget.18668
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000410284800026
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85029782397
    Appears in Collections:[Chiou-Hwa Yuh] Periodical Articles

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