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J.J. Bigda



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    MINI 34 - RNA and miRNA (ID 162)

    • Event: WCLC 2015
    • Type: Mini Oral
    • Track: Biology, Pathology, and Molecular Testing
    • Presentations: 1
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      MINI34.14 - Biological Role of Prognostic MicroRNAs (MiRNAs) in Squamous Lung Cancer Cell Lines (ID 1171)

      18:30 - 20:00  |  Author(s): J.J. Bigda

      • Abstract
      • Presentation
      • Slides

      Background:
      The benefit from postoperative chemotherapy in non-small cell lung cancer (NSCLC) is modest and there are no reliable tools allowing for individual selection of high-risk patients for this management. We earlier demonstrated that overexpression of three miRNAs: miR-662, -192 and -192* may correlate with the risk of distant relapse in squamous cell lung cancer (SCC) patients undergoing pulmonary resection (Skrzypski et al. 2014, Br J Cancer). However, the role of these miRNAs in maintaining aggressive phenotype and/or chemoresistance of SCC is unknown. The aim of this study was to assess the biological role of three abovementioned miRNAs in SCC cells in vitro.

      Methods:
      In the search for appropriate in vitro model we screened by reverse transcription quantitative PCR 11 NSCLC cell lines (H1703, H520, H662, SK-MES-1, A549, H23, H1975, HCC 827, PC9, H460 and Calu-6) for miRNA expression profiles and analyzed their phenotypic features including migration, invasion and clonogenic potential. H520 and H1703 SCC cell lines were transfected with locked nucleic acid miRNA inhibitors. The sensitivity of transfected and wild type cells to cisplatin and etoposide was compared using cytotoxic MTT test. Soft agar colony formation assay was performed to assess the clonogenic potential of transfected vs. non-transfected cells.

      Results:
      Among the analyzed NSCLC cell lines, H520 cells showed natural overexpression of miR-662, -192 and -192*. These cells were resistant to both chemotherapeutics and exhibited an ability to form colonies in soft agar. The inhibition of miR-662 and miR-192 sensitized these cells to etoposide (p=0.004 and 0.016, respectively) but not to cisplatin. Similar results were obtained for H1703 cells (p=0.002 and 0.02, respectively). H520 cells treated with miR-192 and miR-662 inhibitors, compared to negative control, also demonstrated reduced number of colonies in soft agar (p<0.001).

      Conclusion:
      We developed and optimized a cellular model for in vitro studies of biological role of three prognostic miRNAs in SCC. Genes regulated by miR-662 and/or miR-192 may be involved in maintaining the chemoresistance and clonogenic potential of SCC, and these features may be inhibited in a miR-dependent specific manner. Further studies may elucidate predictive value of these genes and a possibility of their targeting with novel therapeutics.

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