國家衛生研究院 NHRI:Item 3990099045/13229
English  |  正體中文  |  简体中文  |  Items with full text/Total items : 12145/12927 (94%)
Visitors : 914993      Online Users : 1423
RC Version 6.0 © Powered By DSPACE, MIT. Enhanced by NTU Library IR team.
Scope Tips:
  • please add "double quotation mark" for query phrases to get precise results
  • please goto advance search for comprehansive author search
    •  Adv. Search
    Home ‧ Login ‧ Upload ‧ Help ‧ About ‧ Administer Goto mobile version


    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/13229


    Title: RSF1 requires CEBP/Beta and hSNF2H to promote IL-1Beta-mediated angiogenesis: The clinical and therapeutic relevance of RSF1 overexpression and amplification in myxofibrosarcomas
    Other Titles: RSF1 requires CEBP/β and hSNF2H to promote IL-1β-mediated angiogenesis: The clinical and therapeutic relevance of RSF1 overexpression and amplification in myxofibrosarcomas
    Authors: Li, CF;Chan, TC;Wang, CI;Fang, FM;Lin, PC;Yu, SC;Huang, HY
    Contributors: National Institute of Cancer Research
    Abstract: Myxofibrosarcoma is genetically complex and lacks effective nonsurgical treatment strategies; thus, elucidation of novel molecular drivers is urgently needed. Reanalyzing public myxofibrosarcoma datasets, we identified mRNA upregulation and recurrent gain of RSF1 and characterized this chromatin remodeling gene. Myxofibrosarcoma cell lines were employed to elucidate the oncogenic mechanisms of RSF1 by genetic manipulation and two IL-1β-neutralizing antibodies (RD24, P2D7KK), highlighting the regulatory basis and targetability of downstream IL-1β-mediated angiogenesis. Tumor samples were assessed for RSF1, IL-1β, and microvascular density (MVD) by immunohistochemistry and for RSF1 gene status by FISH. In vivo, RSF1-silenced and P2D7KK-treated xenografts were analyzed for tumor-promoting effects and the IL-1β-linked therapeutic relevance of RSF1, respectively. In vitro, RSF1 overexpression promoted invasive and angiogenic phenotypes with a stronger proangiogenic effect. RT-PCR profiling identified IL1B as a top-ranking candidate upregulated by RSF1. RSF1 required hSNF2H and CEBP/β to cotransactivate the IL1B promoter, which increased the IL1B mRNA level, IL-1β secretion and angiogenic capacity. Angiogenesis induced by RSF1-upregulated IL-1β was counteracted by IL1B knockdown and both IL-1β-neutralizing antibodies. Clinically, RSF1 overexpression was highly associated with RSF1 amplification, IL-1β overexpression, increased MVD and higher grades (all P ≤ 0.01) and independently predicted shorter disease-specific survival (P = 0.019, hazard ratio: 4.556). In vivo, both RSF1 knockdown and anti-IL-1β P2D7KK (200 μg twice weekly) enabled significant growth inhibition and devascularization in xenografts. In conclusion, RSF1 overexpression, partly attributable to RSF1 amplification, contributes a novel proangiogenic function by partnering with CEBP/β to cotransactivate IL1B, highlighting its prognostic, pathogenetic, and therapeutic relevance in myxofibrosarcomas.
    Date: 2021-04
    Relation: Angiogenesis. 2021 Aug;24(3):533-548.
    Link to: http://dx.doi.org/10.1007/s10456-020-09764-4
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0969-6970&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000611923300001
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85099915965
    Appears in Collections:[Others] Periodical Articles

    Files in This Item:

    File Description SizeFormat
    SCP85099915965.pdf5079KbAdobe PDF201View/Open


    All items in NHRI are protected by copyright, with all rights reserved.

    Related Items in TAIR

    DSpace Software Copyright © 2002-2004  MIT &  Hewlett-Packard  /   Enhanced by   NTU Library IR team Copyright ©   - Feedback