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

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

Content Provider	Semantic Scholar
Author	Pan, Banzhou Chen, Yitian Song, Hai-Zhu Xu, Yichen Wang, Rui Chen, Longbang
Copyright Year	2015
Abstract	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.
Starting Page	317
Ending Page	331
Page Count	15
File Format	PDF HTM / HTML
Alternate Webpage(s)	http://www.oncotarget.com/index.php?journal=oncotarget&op=download&page=article&path%5B%5D=2787&path%5B%5D=5259
PubMed reference number	25426560v1
Volume Number	6
Journal	Oncotarget
Language	English
Access Restriction	Open
Subject Keyword	Autophagy Chromosome 3 Short Arm Cisplatin Down-Regulation EBV-BART10-3p microRNA Etoposide Maxillary right first molar prosthesis MicroRNAs Neoplasms Small cell carcinoma of lung VP-16 cellular targeting pediatric intracranial germ cell brain tumor
Content Type	Text
Resource Type	Article

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