國家衛生研究院 NHRI:Item 3990099045/9472
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    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/9472


    Title: Negative feedback regulation of AXL by miR-34a modulates apoptosis in lung cancer cells
    Authors: Cho, CY;Huang, JS;Shiah, SG;Chung, SY;Lay, JD;Yang, YY;Lai, GM;Cheng, AL;Chen, LT;Chuang, SE
    Contributors: National Institute of Cancer Research
    Abstract: The AXL receptor tyrosine kinase is frequently overexpressed in cancers and is important in cancer invasion/metastasis and chemoresistance. Here, we demonstrate a regulatory feedback loop between AXL and microRNA (miRNA) at the post-transcriptional level. Both the GAS6-binding domain and the kinase domain of AXL, particularly the Y779 tyrosine phosphorylation site, are shown to be crucial for this autoregulation. To clarify the role of miRNAs in this regulation loop, approaches using bioinformatics and molecular techniques were applied, revealing that miR-34a may target the 3' UTR of AXL mRNA to inhibit AXL expression. Interestingly and importantly, AXL overexpression may induce miR-34a expression by activating the transcription factor ELK1 via the JNK signaling pathway. In addition, ectopic overexpression of ELK1 promotes apoptosis through, in part, down-regulation of AXL. Therefore, we propose that AXL is autoregulated by miR-34a in a feedback loop; this may provide a novel opportunity for developing AXL-targeted anticancer therapies.
    Date: 2016-02
    Relation: RNA. 2016 Feb;22(2):303-315.
    Link to: http://dx.doi.org/10.1261/rna.052571.115
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1355-8382&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000369775400013
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84956826470
    Appears in Collections:[Shuang-En Chuang] Periodical Articles
    [Li-Tzong Chen] Periodical Articles
    [Gi-Ming Lai(2004-2008)] Periodical Articles
    [Shine-Gwo Shiah] Periodical Articles

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