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 |
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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. |
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ISSN: | 1178-6930 1178-6930 |
DOI: | 10.2147/OTT.S165290 |