Open Access

Tumor‑released lncRNA H19 promotes gefitinib resistance via packaging into exosomes in non‑small cell lung cancer

  • Authors:
    • Yi Lei
    • Wang Guo
    • Bowang Chen
    • Lu Chen
    • Jiaxin Gong
    • Weimin Li
  • View Affiliations

  • Published online on: October 3, 2018     https://doi.org/10.3892/or.2018.6762
  • Pages: 3438-3446
  • Copyright: © Lei et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Currently, resistance to tyrosine kinase inhibitors, such as gefitinib, has become one major obstacle for improving the clinical outcome of patients with metastatic and advanced‑stage non‑small cell lung cancer (NSCLC). While cell behavior can be modulated by long non‑coding RNAs (lncRNAs), the contributions of lncRNAs within extracellular vesicles (exosomes) are largely unknown. To this end, the involvement and regulatory functions of lncRNA H19 wrapped by exosomes during formation of gefitinib resistance in human NSCLC were investigated. Gefitinib‑resistant cell lines were built by continuously grafting HCC827 and HCC4006 cells into gefitinib‑contained culture medium. RT‑qPCR assays indicated that H19 was increased in gefitinib‑resistant cells when compared to sensitive parent cells. Functional experiments revealed that silencing of H19 potently promoted gefitinib‑induced cell cytotoxicity. H19 was secreted by packaging into exosomes and this packaging process was specifically mediated by hnRNPA2B1. H19 wrapped in exosomes could be transferred to non‑resistant cells, thus inducing gefitinib resistance. Moreover, treatment‑sensitive cells with exosomes highly‑expressing H19 induced gefitinib resistance, while knockdown of H19 abrogated this effect. In conclusion, H19 promoted gefitinib resistance of NSCLC cells by packaging into exosomes. Therefore, exosomal H19 may be a promising therapeutic target for EGFR+ NSCLC patients.
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December-2018
Volume 40 Issue 6

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Lei Y, Guo W, Chen B, Chen L, Gong J and Li W: Tumor‑released lncRNA H19 promotes gefitinib resistance via packaging into exosomes in non‑small cell lung cancer. Oncol Rep 40: 3438-3446, 2018
APA
Lei, Y., Guo, W., Chen, B., Chen, L., Gong, J., & Li, W. (2018). Tumor‑released lncRNA H19 promotes gefitinib resistance via packaging into exosomes in non‑small cell lung cancer. Oncology Reports, 40, 3438-3446. https://doi.org/10.3892/or.2018.6762
MLA
Lei, Y., Guo, W., Chen, B., Chen, L., Gong, J., Li, W."Tumor‑released lncRNA H19 promotes gefitinib resistance via packaging into exosomes in non‑small cell lung cancer". Oncology Reports 40.6 (2018): 3438-3446.
Chicago
Lei, Y., Guo, W., Chen, B., Chen, L., Gong, J., Li, W."Tumor‑released lncRNA H19 promotes gefitinib resistance via packaging into exosomes in non‑small cell lung cancer". Oncology Reports 40, no. 6 (2018): 3438-3446. https://doi.org/10.3892/or.2018.6762