國家衛生研究院 NHRI:Item 3990099045/8009
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    題名: Suppression of dicer increases sensitivity to gefitinib in human lung cancer cells
    作者: Chen, JC;Su, YH;Chiu, CF;Chang, YW;Yu, YH;Tseng, CF;Chen, HA;Su, JL
    貢獻者: National Institute of Cancer Research
    摘要: BACKGROUND: Accumulating evidence is revealing an important role of microRNA (miRNA) in tumor progression and chemotherapeutic resistance. Dicer is a cytoplasmic endoribonuclease type III crucial for production of mature miRNAs. The aberrant expression of Dicer has also been reportedly associated with clinical aggressiveness, prognosis, and patient survival in various cancer types. However, the molecular mechanisms of Dicer in acquired gefitinib resistance are still not clear. METHODS: In this study, we analyzed the protein level of Dicer between gefitinib-sensitive (PC9) and gefitinib-resistant (PC9/GR) non-small-cell lung cancer (NSCLC) cell lines by Western blot analysis. Silence and overexpression of the Dicer were performed to investigate the effects on gefitinib sensitivity, as assessed by (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay and sub-G1 assay of flow cytometry. To further explore the mechanism of chemoresistance, we examined whether Dicer knockdown led to modulating specific miRNAs and its miRNA target genes. RESULTS: Dicer expression was significantly increased in PC9/GR compared with PC9 cells. Knockdown of Dicer restores gefitinib sensitivity in resistant cells, and overexpression of Dicer enhances resistance to gefitinib in sensitive cells. Silencing of Dicer induces sensitivity to gefitinib in NSCLC cells through the downregulation of miR-30b/c and miR-221/222 to increase the protein level of caspase-3, resulting in an increase in gefitinib-induced apoptosis. CONCLUSIONS: Dicer contributes to the resistance to gefitinib in lung cancer. These results indicate that Dicer may be a target for diagnosis and therapy of patients with resistance to gefitinib.
    日期: 2014-12
    關聯: Annals of Surgical Oncology. 2014 Dec;21(4 Suppl.):555-563.
    Link to: http://dx.doi.org/10.1245/s10434-014-3673-y
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1068-9265&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000345320300021
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84939882280
    顯示於類別:[蘇振良] 期刊論文

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