Open Access

Autophagy inhibition and microRNA‑199a‑5p upregulation in paclitaxel‑resistant A549/T lung cancer cells

  • Authors:
    • Tianjiao Zeng
    • Mingshi Xu
    • Wanli Zhang
    • Xiaofan Gu
    • Fangqing Zhao
    • Xuan Liu
    • Xiongwen Zhang
  • View Affiliations

  • Published online on: June 1, 2021     https://doi.org/10.3892/or.2021.8100
  • Article Number: 149
  • Copyright: © Zeng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Multidrug resistance (MDR) is one of the major reasons for the clinical failure of cancer chemotherapy. Autophagy activation serves a crucial role in MDR. However, the specific molecular mechanism linking autophagy with MDR remains unknown. The results of the present study demonstrated that autophagy was inhibited and microRNA (miR)‑199a‑5p levels were upregulated in MDR model lung cancer cells (A549/T and H1299/T) compared with those in the parental cell lines. Paclitaxel (PTX) treatment increased the expression levels of miR‑199a‑5p in parental lung cancer cells compared with those in PTX‑untreated cells, and these expression levels were negatively correlated with PTX sensitivity of the cells. miR‑199a‑5p knockdown in A549/T cells induced autophagy and resensitized cells to multiple chemotherapeutic drugs including PTX, taxotere, topotecan, SN38, oxaliplatin and vinorelbine. By contrast, miR‑199a‑5p overexpression in A549 cells suppressed autophagy and desensitized cells to these chemotherapeutic drugs. Mechanistically, the results of the present study demonstrated that miR‑199a‑5p blocked autophagy by activating the PI3K/Akt/mTOR signaling pathway and inhibiting the protein expression of autophagy‑related 5. Furthermore, p62 protein was identified as a direct target of miR‑199a‑5p; miR‑199a‑5p bound to p62 mRNA to decrease its mRNA and protein expression levels. In conclusion, the results of the present study suggested that miR‑199a‑5p may contribute to MDR development in lung cancer cells by inhibiting autophagy and targeting p62. The regulatory effect of miR‑199a‑5p on autophagy may provide novel insights for future multidrug‑resistant lung cancer chemotherapy.
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July-2021
Volume 46 Issue 1

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

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Copy and paste a formatted citation
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Spandidos Publications style
Zeng T, Xu M, Zhang W, Gu X, Zhao F, Liu X and Zhang X: Autophagy inhibition and microRNA‑199a‑5p upregulation in paclitaxel‑resistant A549/T lung cancer cells. Oncol Rep 46: 149, 2021.
APA
Zeng, T., Xu, M., Zhang, W., Gu, X., Zhao, F., Liu, X., & Zhang, X. (2021). Autophagy inhibition and microRNA‑199a‑5p upregulation in paclitaxel‑resistant A549/T lung cancer cells. Oncology Reports, 46, 149. https://doi.org/10.3892/or.2021.8100
MLA
Zeng, T., Xu, M., Zhang, W., Gu, X., Zhao, F., Liu, X., Zhang, X."Autophagy inhibition and microRNA‑199a‑5p upregulation in paclitaxel‑resistant A549/T lung cancer cells". Oncology Reports 46.1 (2021): 149.
Chicago
Zeng, T., Xu, M., Zhang, W., Gu, X., Zhao, F., Liu, X., Zhang, X."Autophagy inhibition and microRNA‑199a‑5p upregulation in paclitaxel‑resistant A549/T lung cancer cells". Oncology Reports 46, no. 1 (2021): 149. https://doi.org/10.3892/or.2021.8100