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Autophagy is a regulator of TRAIL-induced apoptosis in NSCLC A549 cells

  • RESEARCH ARTICLE
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Journal of Cell Communication and Signaling Aims and scope

Abstract

Autophagy, a catabolic process by which cytoplasmic components are degraded in lysosomes, plays an important role in the maintenance of cellular homeostasis. Dysregulation of autophagy is associated with several diseases. However, few studies have addressed the role of autophagy in the lung, and its role in lung diseases remains unclear. In the present study, we examined the effect of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) on autophagy in A549 cells and explored the underlying mechanisms. We showed that TRAIL promoted autophagosome formation, as detected by the levels of LC3-II, and its effect on promoting autophagy was dependent on the expression of the autophagy related genes (ATGs) Atg5, Atg7, and beclin-1. TRAIL-induced ATG expression was attenuated by JNK silencing or treatment with the JNK inhibitor SP600125, indicating the involvement of the JNK pathway. Crosstalk between autophagy and apoptosis was demonstrated by silencing the autophagy related genes Atg5, Atg7, and beclin-1, and the dependence of TRAIL-induced apoptosis on autophagy-related gene expression. Taken together, our results indicate that TRAIL promotes autophagy in A549 cells via a mechanism involving the modulation of ATG expression through the JNK pathway. Inhibition of autophagy enhanced TRAIL-induced cell proliferative inhibition and apoptosis in A549 cells.

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Abbreviations

TRAIL:

tumor necrosis factor-related apoptosis-inducing ligand

ATGs:

autophagy related genes

JNK:

c-Jun terminal kinase

FADD:

Fas-associated death domain protein

COPD:

chronic obstructive lung disease

siRNA:

Small interfering RNA

siCon:

Small interfering RNA control.

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Acknowledgments

This work was financially supported by National Nature Science Foundation of China (no. 81300005).

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Authors and Affiliations

  1. Department of Respiratory, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road, Shanghai, 200080, China

    Yuqing Chen, Xin Zhou & Aihua Bao

  2. Department of Respiratory, Shanghai Nine people’s Hospital, Shanghai JiaoTong University School of Medicine, 639 Manufacturing bureau road, Shanghai, 200011, China

    Jianou Qiao

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  1. Yuqing Chen
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  2. Xin Zhou
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  3. Jianou Qiao
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  4. Aihua Bao
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Correspondence to Yuqing Chen.

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Chen, Y., Zhou, X., Qiao, J. et al. Autophagy is a regulator of TRAIL-induced apoptosis in NSCLC A549 cells. J. Cell Commun. Signal. 11, 219–226 (2017). https://doi.org/10.1007/s12079-016-0364-4

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  • DOI: https://doi.org/10.1007/s12079-016-0364-4

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