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J Cell Mol Med ; 23(3): 1852-1864, 2019 03.
Article in English | MEDLINE | ID: mdl-30515972

ABSTRACT

Long noncoding RNAs (lncRNAs) are involved in the pathology of various tumours, including non-small cell lung cancer (NSCLC). However, the underlying molecular mechanisms of their specific association with NSCLC have not been fully elucidated. Here, we report that a cytoplasmic lncRNA, DUXAP9-206 is overexpressed in NSCLC cells and closely related to NSCLC clinical features and poor patient survival. We reveal that DUXAP9-206 induced NSCLC cell proliferation and metastasis by directly interacting with Cbl-b, an E3 ubiquitin ligase, and reducing the degradation of epidermal growth factor receptor (EGFR) and thereby augmenting EGFR signaling in NSCLC. Notably, correlations between DUXAP9-206 and activated EGFR signaling were also validated in NSCLC patient specimens. Collectively, our findings reveal the novel molecular mechanisms of DUXAP9-206 in mediating the progression of NSCLC and DUXAP9-206 may serve as a potential target for NSCLC therapy.


Subject(s)
Adaptor Proteins, Signal Transducing/metabolism , Biomarkers, Tumor/metabolism , Carcinoma, Non-Small-Cell Lung/secondary , Gene Expression Regulation, Neoplastic , Lung Neoplasms/pathology , Proto-Oncogene Proteins c-cbl/metabolism , RNA, Long Noncoding/genetics , Adaptor Proteins, Signal Transducing/genetics , Animals , Apoptosis , Biomarkers, Tumor/genetics , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/metabolism , Cell Movement , Cell Proliferation , ErbB Receptors/genetics , ErbB Receptors/metabolism , Female , Humans , Lung Neoplasms/genetics , Lung Neoplasms/metabolism , Mice , Mice, Inbred BALB C , Mice, Nude , Prognosis , Proto-Oncogene Proteins c-cbl/genetics , Survival Rate , Tumor Cells, Cultured , Xenograft Model Antitumor Assays
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