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Xican Gao



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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
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      P2.01-25 - MicroRNA-330-3p Promotes Brain Metastasis of Non-Small Cell Lung Cancer by Activating MAPK/MEK/ERK Signaling Through GRIA3 (ID 14329)

      16:45 - 18:00  |  Author(s): Xican Gao

      • Abstract
      • Slides

      Background

      Brain metastasis (BM) is associated with poor prognosis, recurrence, and death in patients with NSCLC. Discovery and development of biomarkers and elucidation of the mechanism underlying BM in NSCLC is critical for effective prophylactic interventions. MicroRNAs (miRNAs) play an essential role in the development of NSCLC. We investigated miRNAs that serve as biomarkers to differentiate NSCLC patients with and without BM, and explored the underlying mechanism.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Logistic regression was conducted in 122 NSCLC patients (60 without BM, 62 with BM) to examine the association between miRNAs and BM. Stable over-expression and knock-down of miR-330-3p in NSCLC cells was constructed with lentivirus. Expression levels of miR-330-3p in NSCLC cells were quantified by quantitive real-time PCR (qRT-PCR). The effects of miR-330-3p on NSCLC cells were investigated using assays of cell viability, migration, invasion, cell cycle, apoptosis, western blotting, immunohistochemical and immunofluorescence staining. A xenograft nude mouse model and in situ brain metastasis model were used to observe tumor growth and brain metastasis. The potential target of miR-330-3p in NSCLC cells was explored using the luciferase reporter assay, qRT-PCR, and western blotting. The miR-330-3p targets were identified using bioinformatics analysis and verified by luciferase reporter assay.

      4c3880bb027f159e801041b1021e88e8 Result

      High serum miR-330-3p was an independent risk for BM. Tissue miR-330-3p was also higher in subjects with BM (P=0.003). Migration and invasiveness were increased by over-expressing miR-330-3p using a lentivirus, and decreased by miR-330-3p knockdown in both cell lines. In nude mice receiving NSCLC cells, either subcutaneously or into the brain, tumor growth was faster in mice receiving cells permanently expressing exogenous miR-330-3p, and slower in cells expressing the anti-miR-330-3p sequence. Bioinformatics analysis, followed by microarray analysis of A549 cells over-expressing miR-330-3p and luciferase reporter assay suggested the glutamate receptor GRIA3 as a target of miR-330-3p. Experiments using selective kinase inhibitors suggested that GRIA3 is regulated by miR-330-3p via MAPK/MEK/ERK signaling pathway.

      8eea62084ca7e541d918e823422bd82e Conclusion

      miR-330-3p promotes NSCLC brain metastasis possibly in part via the MAPK/MEK/ERK pathway and GRIA3, and might be a potential target for the further research of NSCLC brain metastasis.

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