Research Papers:

Mir-24-3p downregulation contributes to VP16–DDP resistance in small-cell lung cancer by targeting ATG4A

Banzhou Pan, Yitian Chen, Haizhu Song, Yichen Xu, Rui Wang and Longbang Chen _

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Oncotarget. 2015; 6:317-331. https://doi.org/10.18632/oncotarget.2787

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Banzhou Pan1*, Yitian Chen1*, Haizhu Song1, Yichen Xu1, Rui Wang1 and Longbang Chen1

1 Department of Medical Oncology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China

* Co-first authors


Longbang Chen, email:

Keywords: miR-24-3p, autophagy, chemoresistance, small-cell lung cancer, mechanism, ATG4A

Received: September 15, 2014 Accepted: November 15, 2014 Published: November 16, 2014


Although the combination of etoposide (VP16) and cisplatin (DDP) is widely used as a first-line treatment for advanced-stage small-cell lung cancer (SCLC), chemoresistance limits its clinical use. Abnormalities of autophagy are associated with tumor chemoresistance. The present study found that miR-24-3p, a recently discovered microRNA, is significantly downregulated in VP16–DDP-resistant SCLC cells (H446/EP) compared with VP16–DDP-sensitive parent cells (H446). Forced expression of miR-24-3p sensitized H446/EP cells to VP16–DDP treatment because of a blockade of autophagic activity. We further found that downregulated miR-24-3p enhanced autophagy activation as it directly targets and inhibits autophagy-associated gene 4A (ATG4A). Overexpression of miR-24-3p into H446/EP cells led to reduction of the ATG4A protein level, allowing SCLC cells to resensitize to VP16–DDP. We conclude that miR-24-3p regulates autophagy by targeting ATG4A. Inhibition of autophagy by increasing miR-24-3p could be the basis of a strategy to prevent and treat SCLC with combination chemotherapy, particularly in chemoresistant disease.

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