Cited by 103MicroRNA in disease regulationAutophagy in Disease and TherapyLung Cancer Research Studies

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

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Pan, Banzhou, Chen, Yitian, Song, Haizhu, Xu, Yichen, Wang, Rui, Chen, Longbang·2015·Oncotarget

Abstract

// Banzhou Pan 1* , Yitian Chen 1* , Haizhu Song 1 , Yichen Xu 1 , Rui Wang 1 and Longbang Chen 1 1 Department of Medical Oncology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China * Co-first authors Correspondence: 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 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.

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Authors
Pan, B., Chen, Y., Song, H., Xu, Y., Wang, R., & Chen, L.
Affiliations
Nanjing General Hospital of Nanjing Military Command (CN)
Corresponding author
  • Pan, Banzhou
  • Chen, Yitian
Venue
Oncotarget
Published
2014-11-16
Volume
6
Issue
1
Pages
317-331
ISSN
1949-2553 (ISSN-L)
OpenAlex
W1484891738
Cited by
103
References
44
Citations by year
2026: 2 · 2025: 6 · 2024: 3 · 2023: 5 · 2022: 14 · 2021: 11 · 2020: 18 · 2019: 7 · 2018: 5 · 2017: 14 · 2016: 12 · 2015: 6
FWCI
3.42
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Oncotarget (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • National Natural Science Foundation of China (81301914, 81402492, 81172106, 81071806)
  • Government of Jiangsu Province
  • Natural Science Foundation of Jiangsu Province
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
  • Health Sciences › Medicine › Oncology › Lung Cancer Research Studies
Keywords
miR-24-3p, ATG4A, small cell lung cancer, chemoresistance, etoposide, cisplatin, autophagy, microRNA, combination chemotherapy, drug resistance reversal
MeSH terms
Autophagy-Related Proteins, Autophagy, Cell Survival, Cisplatin, Cysteine Endopeptidases, Etoposide, Humans, Lung Neoplasms, Transfection, Blotting, Western, Down-Regulation, Gene Expression Regulation, Neoplastic, Apoptosis, Drug Resistance, Neoplasm, RNA, Small Interfering, MicroRNAs, Cell Line, Tumor, Small Cell Lung Carcinoma, Real-Time Polymerase Chain Reaction

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