Author of

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  P3.02 - Poster Session 3 - Novel Cancer Genes and Pathways (ID 149)

  • Event: WCLC 2013
  • Type: Poster Session
  • Track: Biology
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/30/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

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    P3.02-008 - TRIM14 is a Novel Tumor Suppressor Gene in Non-Small-Cell Lung Cancer (ID 1204)

    09:30 - 09:30  |  Author(s): J. Hai
    • Abstract

    Background
    Non-small-cell lung carcinoma (NSCLC) accounts for 85% of all malignant lung tumors. Our group previously identified Tripartite Motif-Containing 14 (TRIM14) as a component of a prognostic multigene expression signature for NSCLC patients. TRIM14 belongs to a conserved family of Tripartite Motif-encoding genes involved in a broad range of biological processes, such as transcriptional regulation, cell proliferation, and apoptosis. However, TRIM14 itself is poorly understood. Here we investigate the functional and prognostic role of TRIM14 in NSCLC.

    Methods
    Cox proportional hazards regression analysis was done on published mRNA expression datasets of primary NSCLCs to identify whether TRIM14 expression is associated with patient survival. The expression of TRIM14 was modified in human NSCLC cell lines (NCI-H1395, NCI-H1650, NCI-H520 and NCI-H157) by lentivirus-mediated overexpression and short-hairpin RNA (shRNA)-mediated silencing. Effects were assessed by examining in vitro cell proliferation and anchorage-independent growth, and in vivo tumorigenicity in mice.

    Results
    Univariate analyses demonstrated that TRIM14 expression is significantly associated with patient survival, with loss of expression correlated with poorer prognosis in resectable early stage NSCLC patients. In vitro studies showed that TRIM14 overexpression in H1395 cells suppressed proliferation and anchorage-independent growth, whereas shRNA knockdown of TRIM14 expression in H1650, H520, and H157 cells promoted cell proliferation and colony formation. In vivo studies demonstrated that suppressing TRIM14 expression in H1650 and H157 cells significantly promotes tumor growth in immunodeficient mice.

    Conclusion
    We show that TRIM14 may function as a tumor suppressor gene in NSCLC affecting cell proliferation and anchorage-independent growth in vitro and tumor growth in mice. We provide evidence that prognostic genes identified in microarray based gene expression analyses may have a strong biological rationale.