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W. Song



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    OA 18 - Lung Cancer Pathology and Genetics (ID 687)

    • Event: WCLC 2017
    • Type: Oral
    • Track: Biology/Pathology
    • Presentations: 1
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      OA 18.08 - FLI1 Circular RNAs Promote Metastasis of Small Cell Lung Cancer Cells by Direct Binding to miR-584-3p (ID 8894)

      15:45 - 15:55  |  Author(s): W. Song

      • Abstract
      • Presentation
      • Slides

      Background:
      Small cell lung cancer (SCLC) is regarded as the most devastative type of human lung malignancies, with their rapid growth and we have discovered that there are FLI1 circular RNAs (circFLI1s) aberrantly expressed in SCLC tissues, such as circFLI1E2-4 and circFLI1E2-5 which are derived from exon 2-exon 4 and exon 2-exon 5 of FLI1, respectively. This study investigated the role of circFLI1s in the biological processes of SCLC.

      Method:
      The expression level of circFLI1s was evaluated by fluorescence in situ hybridization(FISH) in 54 primary SCLC and 50 non-small cell lung cancer (NSCLC) patients with known follow-up data. Correlation between circFLI1s expression and clinical characteristics was assessed with logistic regression. Cellular proliferation, apoptosis, cell cycle, migration and ability of colony formation were used to investigate the function of circFLI1s in SCLC. Ulteriorly, we explored the possible mechanism of circFLI1s via luciferase reporter assay, RT-PCR and FISH.

      Result:
      The expression of circFLI1E2-4 and circFLI1E2-5 were up-regulated in SCLC tissues compared with NSCLC tissues . The high expression of these circFLI1s was significantly associated with positive lymph nodal involvement (p < 0.05). The silencing of circFLI1E2-4 and circFLI1E2-5 but not FLI1 mRNA significantly inhibited migration of highly aggressive SCLC cell lines in vitro and vivo, while did not affect their proliferation, cell cycle, apoptosis and colony formation. Via bioinformatic analysis and luciferase screening assay, circFLI1s were observed to sponge to 2 miRNAs with 6 potential binding sites. Specifically, we showed that these circFLI1s directly binded to miR-584-3p and inhibited miR-584-3p activity, further to regulate the transcriptional activity of its target gene ROCK1 and the RhoA/ROCK1 signal pathway.

      Conclusion:
      This study uncovers that circFLI1s is an important driving factor that promotes tumor metastasis in SCLC through , and may serve as an attractive target for therapeutic intervention of SCLC.

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