國家衛生研究院 NHRI:Item 3990099045/12450
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    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/12450


    Title: Epigenetic silencing of ubiquitin specific protease 4 by snail1 contributes to macrophage-dependent inflammation and therapeutic resistance in lung cancer
    Authors: Lai, CY;Yeh, DW;Lu, CH;Liu, YL;Chuang, YC;Ruan, JW;Kao, CY;Huang, LR;Chuang, TH
    Contributors: Immunology Research Center;Institute of Molecular and Genomic Medicine
    Abstract: There is a positive feedback loop driving tumorigenesis and tumor growth through coordinated regulation of epigenetics, inflammation, and stemness. Nevertheless, the molecular mechanism linking these processes is not well understood. In this study, we analyzed the correlation of de-ubiquitinases (DUBs) expression with survival data from the OncoLnc database. Among the DUBs analyzed, ubiquitin specific protease 4 (USP4) had the lowest negative Cox coefficient. Low expression of USP4 was associated with poor survival among lung cancer patients and was inversely correlated with expression of stemness and inflammation markers. Expression of USP4 were reduced at more advanced stages of lung cancer. Mechanistically, expression of USP4 was downregulated in snail1-overexpressing and stemness-enriched lung cancer cells. Snail1 was induced in lung cancer cells by interaction with macrophages, and epigenetically suppressed USP4 expression by promoter methylation. Stable knockdown of USP4 in lung cancer cells enhanced inflammatory responses, stemness properties, chemotherapy resistance, and the expression of molecules allowing escape from immunosurveillance. Further, mice injected with USP4 knockdown lung cancer cells demonstrated enhanced tumorigenesis and tumor growth. These results reveal that the Snail1-mediated suppression of USP4 is a potential mechanism to orchestrate epigenetic regulation, inflammation and stemness for macrophage-promoted tumor progression.
    Date: 2020-01-08
    Relation: Cancers. 2020 Jan 8;12(1):Article number 148.
    Link to: http://dx.doi.org/10.3390/cancers12010148
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=2072-6694&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000516826700148
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85077839059
    Appears in Collections:[Tsung-Hsien Chuang] Periodical Articles
    [Cheng-Yuan Gao] Periodical Articles
    [Li-Rung Huang] Periodical Articles

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