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Article

Decreased human antigen R expression confers resistance to tyrosine kinase inhibitors in epidermal growth factor receptor-mutant lung cancer by inhibiting Bim expression

  • Authors:
    • Yunfeng Yao
    • Huili Chu
    • Jun Wang
    • Baocheng Wang
  • View Affiliations / Copyright

    Affiliations: Institute of Post‑Graduate, The Second Military Medical University, People's Liberation Army, Shanghai 200433, P.R. China, Department of Oncology, General Hospital, Jinan Command of The People's Liberation Army, Jinan, Shandong 250031, P.R. China, Institute of Post‑Graduate, The Second Military Medical University, People's Liberation Army, Shanghai 200433, P.R. China
  • Pages: 2930-2942
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    Published online on: August 22, 2018
       https://doi.org/10.3892/ijmm.2018.3835
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Abstract

Primary resistance to epidermal growth factor receptor‑tyrosine kinase inhibitors (EGFR‑TKIs) is an obstacle for the treatment of non‑small cell lung cancer (NSCLC); however, the associated mechanisms are not well understood. Studies have reported that Bim expression levels may be associated with the efficacy of EGFR‑TKI treatment in NSCLC patients harboring EGFR mutations. Human antigen R (HuR) regulates the mRNA and protein expression of target genes, including certain B‑cell lymphoma 2 family members. The present study investigated whether HuR mediates resistance to EGFR‑TKIs via the regulation of Bim. The results demonstrated that decreased levels of HuR and Bim protein expression are associated with primary resistance to EGFR‑TKIs and reduced median progression‑free survival in NSCLC patients. In vitro assays also revealed that knockdown of HuR resulted in primary EGFR‑TKI resistance and reduced gefitinib‑induced apoptosis in HCC827 cells by decreasing Bim expression. Furthermore, elevated HuR expression restored gefitinib sensitivity and enhanced gefitinib‑induced apoptosis in H1650 cells by increasing Bim expression. In vivo, it was further demonstrated that overexpression of HuR was able to restore the gefitinib sensitivity of H1650 cells. Therefore, altered HuR/Bim expression is proposed to be a novel mechanism of EGFR‑TKI resistance in NSCLC.
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Copy and paste a formatted citation
Spandidos Publications style
Yao Y, Chu H, Wang J and Wang B: Decreased human antigen R expression confers resistance to tyrosine kinase inhibitors in epidermal growth factor receptor-mutant lung cancer by inhibiting Bim expression. Int J Mol Med 42: 2930-2942, 2018.
APA
Yao, Y., Chu, H., Wang, J., & Wang, B. (2018). Decreased human antigen R expression confers resistance to tyrosine kinase inhibitors in epidermal growth factor receptor-mutant lung cancer by inhibiting Bim expression. International Journal of Molecular Medicine, 42, 2930-2942. https://doi.org/10.3892/ijmm.2018.3835
MLA
Yao, Y., Chu, H., Wang, J., Wang, B."Decreased human antigen R expression confers resistance to tyrosine kinase inhibitors in epidermal growth factor receptor-mutant lung cancer by inhibiting Bim expression". International Journal of Molecular Medicine 42.5 (2018): 2930-2942.
Chicago
Yao, Y., Chu, H., Wang, J., Wang, B."Decreased human antigen R expression confers resistance to tyrosine kinase inhibitors in epidermal growth factor receptor-mutant lung cancer by inhibiting Bim expression". International Journal of Molecular Medicine 42, no. 5 (2018): 2930-2942. https://doi.org/10.3892/ijmm.2018.3835
Copy and paste a formatted citation
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Spandidos Publications style
Yao Y, Chu H, Wang J and Wang B: Decreased human antigen R expression confers resistance to tyrosine kinase inhibitors in epidermal growth factor receptor-mutant lung cancer by inhibiting Bim expression. Int J Mol Med 42: 2930-2942, 2018.
APA
Yao, Y., Chu, H., Wang, J., & Wang, B. (2018). Decreased human antigen R expression confers resistance to tyrosine kinase inhibitors in epidermal growth factor receptor-mutant lung cancer by inhibiting Bim expression. International Journal of Molecular Medicine, 42, 2930-2942. https://doi.org/10.3892/ijmm.2018.3835
MLA
Yao, Y., Chu, H., Wang, J., Wang, B."Decreased human antigen R expression confers resistance to tyrosine kinase inhibitors in epidermal growth factor receptor-mutant lung cancer by inhibiting Bim expression". International Journal of Molecular Medicine 42.5 (2018): 2930-2942.
Chicago
Yao, Y., Chu, H., Wang, J., Wang, B."Decreased human antigen R expression confers resistance to tyrosine kinase inhibitors in epidermal growth factor receptor-mutant lung cancer by inhibiting Bim expression". International Journal of Molecular Medicine 42, no. 5 (2018): 2930-2942. https://doi.org/10.3892/ijmm.2018.3835
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