Mir-24-3p downregulation contributes to VP16-DDP resistance in small-cell lung cancer by targeting ATG4A
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// 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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miR-23a, miR-23b, and miR-24 suppress AMBRA1, ATG12, and ATG4A, respectively.
“For example, miR-23a, miR-23b, and miR-24 suppress AMBRA1 [52], ATG12 [53, 54], and ATG4A [55], respectively.”
From miR-27a and miR-27b regulate autophagic clearance of damaged mitochondria by targeting PTEN-induced putative kinase 1 (PINK1) (2016) · cites this paper as [55]
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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
- Publisher
- Impact Journals, LLC
- Published
- 2014-11-16
- Volume
- 6
- Issue
- 1
- Pages
- 317-331
- ISSN
- 1949-2553 (ISSN-L)
- PMC
- PMC4381597
- 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
- diamond
- doi.org
- 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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