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

Echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase ( ) 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...

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Veröffentlicht in:OncoTargets and therapy 2018-01, Vol.11, p.3649-3657
Hauptverfasser: Yang, Yonghua, Huang, Jingyu, Xie, Nianlin, Huang, Hu, Xu, Shaogan, Cai, Jun, Qi, Shuai
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Sprache:eng
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Zusammenfassung:Echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase ( ) 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 in stem cell-like properties and of lincROR and crizotinib resistance in NSCLC cells are yet to be elucidated. 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. 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. 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.
ISSN:1178-6930
1178-6930
DOI:10.2147/OTT.S165290