lincROR influences the stemness and crizotinib resistance in EML–ALK+ non-small-cell lung cancer cells

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Introduction: Echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase ( EML4–ALK ) is identified as an important pathogenic factor in patients with non-small-cell lung cancer (NSCLC) and could induce a stem-like phenotype in NSCLC cells. Crizotinib is commonly used for EML4–ALK + NSCLC treatment, but its acquired resistance results in tumor recurrence. Long intergenic noncoding RNA, regulator of reprogramming (lincROR) is related to the acquisition and maintenance of self-renewal and stemness features of cancer stem cells. It has been documented that lincROR is implicated in chemoresistance. However, the correlations of lincROR and EML4–ALK in stem cell-like properties and of lincROR and crizotinib resistance in NSCLC cells are yet to be elucidated. Patients and methods: In the present study, we investigated the expression profile of lincROR in EML–ALK NSCLC tissues, and the potential role of lincROR in prognosis was then analyzed. Subsequently, its association with stem cell-like properties of EML–ALK + NSCLC cells was determined. Furthermore, the correlation of lincROR with crizotinib and the effects of lincROR and crizotinib on cell viability of EML4–ALK + NSCLC cells were all explored. Results: The results showed that lincROR expression was upregulated in EML4–ALK + NSCLC tissues relative to EML4–ALK - NSCLC tissues. Low-expressed lincROR was related to a favorable prognosis of patients with EML–ALK NSCLC. lincROR overexpression could enhance the stemness features of EML–ALK + NSCLC cells which were repressed by ALK knockdown. Conclusion: We found that lincROR expression was significantly inhibited because of the increased concentration of crizotinib in EML4–ALK + NSCLC cells. Furthermore, lincROR overexpression increased cell viability of EML4–ALK + NSCLC cells, which was impaired by crizotinib. Conjointly, these results suggested the important role of lincROR in EML–ALK + NSCLC. lincROR may serve as a potential therapeutic target to overcome chemotherapy resistance in EML–ALK + NSCLC. Keywords: EML–ALK, lincROR, stemness, crizotinib, NSCLC

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