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

Yonghua Yang; Jingyu Huang; Nianlin Xie; Hu Huang; Shaogan Xu; Jun Cai; Shuai Qi

doi:10.2147/OTT.S165290

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

Onco Targets Ther. 2018 Jun 22:11:3649-3657. doi: 10.2147/OTT.S165290. eCollection 2018.

Authors

Yonghua Yang^#¹, Jingyu Huang^#², Nianlin Xie^#³, Hu Huang^#⁴, Shaogan Xu⁵, Jun Cai¹, Shuai Qi⁶

Affiliations

¹ Department of Oncology, First Affiliated Hospital of Yangtze University, Jingzhou 434000, Hubei Province, China.
² Department of Thoracic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, Hubei Province, China.
³ Department of Thoracic Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, Shaanxi Province, China.
⁴ Department of Oncology.
⁵ Department of Thoracic Surgery.
⁶ Department of Pharmacy, The 161th Hospital of PLA, Wuhan 430010, Hubei Province, China.

^# Contributed equally.

Abstract

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; NSCLC; crizotinib; lincROR; stemness.