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Promoter methylation of TCF21 may repress autophagy in the progression of lung cancer

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Journal of Cell Communication and Signaling Aims and scope

Abstract

Lung cancer is a leading cause of cancer mortality worldwide. Promoter methylation of transcription factor 21 (TCF21) was frequently observed in the early stage of non-small cell lung cancer (NSCLC). However, clinical relevance and molecular functions of TCF21 in NSCLC progression remain unclear. In this study, we analyzed the associations between TCF21 expression and clinicopathological features in 100 patients with NSCLC and revealed the underlying molecular mechanisms of TCF21 methylation on cell viability, apoptosis and invasion of H1299 cells. We found that the expression of TCF21 was significantly regulated by its methylation level in patients with NSCLC and was associated with tumor stage, metastasis and invasion. Demethylation of H1299 cells by 5-aza-2′-deoxycytine (5-Aza) demonstrated that a higher level of TCF21 expression led to remarkable decreases of cell viability and invasion ability but an increase of cell apoptosis. Accordingly, TCF21 knockdown showed converse results to high expression of TCF21. TCF21 knockdown cells exhibited significantly upregulated ATG-9, BECLIN-1, and LC3-I/II expressions but decreased p62 expression compared to wildtype cells. Inhibition of autophagy by 3-methyladenine (3-MA) elevated TCF21 expression and increased cell apoptosis. TCF21 expression is clinically related to the progress of lung cancer and may inhibit autophagy by suppressing ATG-9 and BECLIN-1. In turn, autophagy may also play an important role in regulation TCF21 expression.

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Abbreviations

TCF21:

transcription factor 21

NSCLC:

non-small cell lung cancer

5-Aza:

5-aza-2′-deoxycytine

3-MA:

3-methyladenine

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Funding

This study was funded by the Science and Technology Development Fund Project of Shenzhen (No. JCYJ 20150403091443278 and JCYJ 20150403091443310).

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Authors and Affiliations

  1. Department of Thoracic Surgery, Peking University Shenzhen Hospital, Lianhua Road No.1120, Shenzhen, Guangdong Province, 518036, China

    Baokun Chen, Chao Zeng, Yiwang Ye, Da Wu, Zhimin Mu, Jixian Liu, Yuancai Xie & Hao Wu

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  1. Baokun Chen
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  2. Chao Zeng
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  3. Yiwang Ye
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  4. Da Wu
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  5. Zhimin Mu
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  7. Yuancai Xie
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  8. Hao Wu
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Correspondence to Hao Wu.

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Chen, B., Zeng, C., Ye, Y. et al. Promoter methylation of TCF21 may repress autophagy in the progression of lung cancer. J. Cell Commun. Signal. 12, 423–432 (2018). https://doi.org/10.1007/s12079-017-0418-2

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  • DOI: https://doi.org/10.1007/s12079-017-0418-2

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