Author of

• 18374

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  P3.02b - Poster Session with Presenters Present (ID 494)

  • Event: WCLC 2016
  • Type: Poster Presenters Present
  • Track: Advanced NSCLC
  • Presentations: 1
  • Moderators:
  • Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)

  • 18495

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    P3.02b-121 - Targeting miR-200c/LIN28B Axis in Acquired EGFR-TKI Resistance Non-Small Cell Lung Cancer Cells Harboring EMT Features (ID 5677)

    14:30 - 14:30  |  Author(s): M. Watanabe
    • Abstract

    Background:
    MicroRNA (miR)-200 family members (miR-200s) are frequently silenced in advanced cancer and have been implicated in the process of epithelial-to-mesenchymal transition (EMT). We previously reported that miR-200s were silenced through promoter methylation in acquired EGFR-tyrosine kinase inhibitor (TKI) resistant non-small cell lung cancer (NSCLC) cells harboring EMT features. In this study, we examined the functional role of miR-200s in NSCLC cells and investigated the novel approach overcoming acquired EGFR-TKI resistance.
    
    Methods:
    We examined miR-200s expressions and promoter methylation statuses in 34 NSCLC cell lines. Then, we analyzed the altered pathway molecules associated with miR-200c statuses using publicly accessible database. Finally, we examined the antitumor effect targeting the molecules related to miR-200s expression in EGFR-TKI sensitive HCC4006 cells and acquired resistance cell line with EMT features HCC4006-GR cells.
    
    Results:
    In the analysis of NSCLC cell lines, miR-200s expression silenced cell lines showed each promoter methylation. There were significant correlations between miR-200c silencing and several oncogenic pathway alterations, including EMT-change and LIN28B overexpression, in database analysis. In addition, EGFR-wild type cell lines showed lower miR-200s expressions compared to EGFR-mutant cell lines. Introduction of miR-200c by using pre-miR-200c caused LIN28B suppression in HCC4006-GR cells. Interestingly, both introduction of miR-200c and knockdown of LIN28B showed antitumor effect in HCC4006-GR cells, whereas they were not effective in parental HCC4006.
    
    Conclusion:
    MiR-200c/LIN28B axis plays an important role in acquired resistance to EGFR-TKI and can be a therapeutic target overcoming drug resistance.