Document Detail


Mir-24-3p downregulation contributes to VP16-DDP resistance in small-cell lung cancer by targeting ATG4A.
MedLine Citation:
PMID:  25426560     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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.
Authors:
Banzhou Pan; Yitian Chen; Haizhu Song; Yichen Xu; Rui Wang; Longbang Chen
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-11-16
Journal Detail:
Title:  Oncotarget     Volume:  -     ISSN:  1949-2553     ISO Abbreviation:  Oncotarget     Publication Date:  2014 Nov 
Date Detail:
Created Date:  2014-11-26     Completed Date:  -     Revised Date:  2014-11-27    
Medline Journal Info:
Nlm Unique ID:  101532965     Medline TA:  Oncotarget     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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