Author of

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  P2.01 - Advanced NSCLC (Not CME Accredited Session) (ID 950)

  • Event: WCLC 2018
  • Type: Poster Viewing in the Exhibit Hall
  • Track:
  • Presentations: 1
  • Moderators:
  • Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall

  • 26923

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    P2.01-118 - LINE-1 Retrotransposition Promotes the Occurrence and Progression of Lung Squamous Cell Carcinoma (ID 12232)

    16:45 - 18:00  |  Author(s): Rui Zhang
    • Abstract

    Background
    

    Retrotransposition is a kind of chromatin rearrangement containing the non-coding region, which makes up about half of the human genome. Long interspersed element-1 (LINE-1) retrotransposition is the only currently known active autonomous transposon in humans and might cause genetic instability, which was reported to occur with high frequency in a variety of tumor tissues. However, the relationship between LINE-1 and lung squamous cell carcinoma (LUSC) is unclear.

    a9ded1e5ce5d75814730bb4caaf49419 Method
    

    We analyzed 504 cases of LUSC samples based on the RNA-seq database in TCGA and screened out 13 LINE-1 retrotransposons with the high occurrence. The somatic LINE-1 retrotransposition were detected in 109 clinical LUSC samples in comparison with their matched adjacent normal tissue samples, as well as the correlation between expression of LINE-1 retrotransposon genes and patients' survival. Then we focused on L1-FGGY and explored its regulation on cell proliferation, apoptosis, migration and invasion in vitro, as well as its roles on promoting tumorigenesis in vivo. We also applied two nonnucleosidic reverse transcriptase inhibitors, nevirapine (NVR) and efavirenz (EFV) both in vitro and in vivo, to investigate whether pharmacological modulation of endogenous reverse transcriptase activity may represent a novel approach in the treatment of LUSC.

    4c3880bb027f159e801041b1021e88e8 Result
    

    We found that 1/3 of tumor samples possessed LINE-1 inserted retrotransposons and the expression of retrotransposon genes in LUSC was significantly higher than that in the corresponding para-carcinoma tissues, indicating that the presence of LINE-1 retrotransposon was related to the occurrence of LUSC. Furthermore, we also found that the survival time of patients with low retrotransposon gene expression was long, while the survival time of patients with high retrotransposon gene expression was short. In this study, we focused on L1-FGGY and further investigated the mechanism of the LINE-1 retrotransposition in regulating the occurrence and progression of LUSC and discovered that the expression of L1-FGGY and FGGY was negatively correlated in LUSC patients. We then discovered that knockdown of FGGY could promote cell proliferation, inhibit cell apoptosis, as well as facilitate cell migration and invasion in vitro. Furthermore, inhibition of FGGY could promote tumorigenesis and tumor metastasis in vivo, which collectively indicated that FGGY might function as a tumor-suppressor gene.

    8eea62084ca7e541d918e823422bd82e Conclusion
    

    We not only uncovered that the LINE-1 retrotransposition L1-FGGY promotes the development of LUSC by inhibiting the expression and function of the tumor-suppressor gene FGGY, but also revealed that LINE-1 retrotransposon might be a new biomarker for early diagnosis, prognosis evaluation, and targeted therapy in the future clinical translation.

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