國家衛生研究院 NHRI:Item 3990099045/7786
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    题名: Up-regulation of mir-92A by stat3 oncogene promotes invasiveness of lung cancer cells
    作者: Hung, WC;Lin, HY;Chiang, CH
    贡献者: National Institute of Cancer Research
    摘要: Background:Signal transducer and activator of transcription 3 (STAT3) activeation is frequently found in human lung cancer and is associated with increased metastasis and reduced survival. The molecular mechanisms by which STAT3 enhances cancer invasion have not been well characterized. Methods: The expression of microRNAs and target genes was measured by real-time RT-PCR. Protein level was studied by Western blotting. Luciferase reporter assay was used to confirm the direct targeting of microRNAs. Gelatin zymography was used to study matrix metalloproteinase (MMP) activity. Transwell assay was used to investigate cell migration and invasion. Results: We find that STAT3 expression is negatively associated with the expression of an endogenous MMPinhibitor, Reversion-inducing Cysteine-rich protein with Kazal motifs (RECK) in a set of lung cancer cell lines. Enforced expression of STAT3 decreases the endogenous MMP inhibitor RECK protein but not mRNA level in H460 cells. Conversely, STAT3 inhibitor S3I-201 increases RECK protein in STAT3-activating H1299 cells.We demonstrate that STAT3 up-regulates miR-92a to repress RECK via post-transcriptional inhibition. RECK 3’UTR reporter activity assay suggests RECK is a direct repression target of miR-92a. Delivery of pre-miR-92a reduces RECK protein level while transfection of anti-miR-92a restores STAT3-induced down-regulation of RECK.Anti-miR-92a attenuates MMPactivity, migration and invasion of H1299 cells and STAT3-overexpressing H460 cells suggesting miR-92a is critical for STAT3-induced invasiveness. Conclusion: we demonstrate that up-regulation of miR-92a by STAT3 is one of the mechanisms by which STAT3 promotes cancer invasion. In addition, we show that RECK is an important mediator of STAT3-induced cell invasiveness. Targeting of the STAT3/miR-92a axis by may be helpful for the treatment of lung cancer.
    日期: 2013-11
    關聯: Respirology. 2013 Nov;18(Suppl. 4):151.
    Link to: http://dx.doi.org/10.1111/resp.12184_27
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1323-7799&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000329292600497
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