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  P3.12 - Small Cell Lung Cancer/NET (Not CME Accredited Session) (ID 978)

  • Event: WCLC 2018
  • Type: Poster Viewing in the Exhibit Hall
  • Track:
  • Presentations: 1
  • Moderators:
  • Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall

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    P3.12-04 - Linc00173 Modulates Chemoresistance of Small Cell Lung Cancer by Binding hnRNPA2B1 and hnRNPI to Regulate CHK2 Level (ID 12469)

    12:00 - 13:30  |  Author(s): Fanrui Zeng
    • Abstract
    • Slides

    Background
    

    Small-cell lung cancer (SCLC), the most aggressive type of lung cancer, accounts for approximately 15% of all lung cancers. Long non-coding RNAs (lncRNAs) with length over 200 nucleotides, have been identified to play crucial regulatory roles in cell differentiation, proliferation, migration, invasion and apoptosis. Long intergenic non-protein coding RNA 173 (Linc00173) which was first identified in small cell lung cancer, and was found to be involved in chemoresistance in our previous array analysis. In this study, we aimed to explore the biological role of Linc00173 and its possible molecular mechanism in SCLC chemoresistance.

    a9ded1e5ce5d75814730bb4caaf49419 Method
    

    Linc00173 was examined in 60 SCLC patient samples by quantitative RT-PCR (qRT-PCR). The functional roles of Linc00173 in SCLC were studied by overexpression and RNA interference approaches in vitro and in vivo. The localization of Linc00173 was studied by separating cytoplasmic and nuclear RNA fractions from SCLC cells. RNA pulldown and mass spectrum experiments were performed to find the RNA-binding proteins that interact with Linc00173. RNA sequencing of RNA-binding proteins-immunoprecipitated RNA and coexpression profiles of Linc00173 and mRNAs were used to identify the gene that was regulated by Linc00173 with the RNA-binding proteins.

    4c3880bb027f159e801041b1021e88e8 Result
    

    Linc00173 expression was significantly associated with chemoresistance and the shorter survival time in SCLC patients. Upregulation of Linc00173 promoted the proliferation and cell-cycle progression and also induced multidrug resistance, whereas downregulation of Linc00173 expression had opposite effects both in vitro and in vivo. Linc00173 increased the expression of hnRNPA2B1 and hnRNPI in the nucleus and formed an RNA-protein complex, which further bound to the target mRNA of CHK2 that is implicated in cell-cycle progression. This interaction made the CHK2 mRNA fragile and decreased its protein level.

    8eea62084ca7e541d918e823422bd82e Conclusion
    

    Linc00173 was first identified to promote proliferation and chemoresistance in SCLC. It interacts directly with hnRNPA2B1 and hnRNPI to regulate levels of CHK2. Overexpression of Linc00173 represents a biomarker of poor prognosis and chemoresistance in SCLC patients.

    6f8b794f3246b0c1e1780bb4d4d5dc53

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