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Cited by 218MicroRNA in disease regulationAutophagy in Disease and TherapyDrug Transport and Resistance Mechanisms

miR-23b-3p regulates the chemoresistance of gastric cancer cells by targeting ATG12 and HMGB2

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An, Y, Zhang, Z, Shang, Y, Jiang, X, Dong, J, Yu, P, Nie, Y, Zhao, Q·2015·Cell Death & Disease
DOI 10.1038/cddis.2015.123PMC PMC4669702
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Abstract

Chemotherapy is an important treatment modality for gastric cancer (GC); however, it usually fails because of drug resistance, especially multidrug resistance (MDR). Previously, we found a novel subset of MDR-associated microRNAs (miRNAs) through high-throughput functional screening. In this report, we investigated the exact roles and mechanisms of miR-23b-3p in the MDR of GC. Using gain or loss-of-function in in vitro and in vivo experiments, we found that overexpression of miR-23b-3p reversed cancer cell resistance to multiple chemotherapeutics in vitro and sensitize tumors to chemotherapy in vivo . Reporter gene assay and western blot analysis showed that ATG12 and HMGB2 were the direct targets of miR-23b-3p. Meanwhile, ATG12 and HMGB2 were positively associated with the occurrence of autophagy. Reducing the expression of these target genes by siRNA or inhibition of autophagy both sensitized GC cells to chemotherapy. These findings suggest that a miR-23b-3p/ATG12/HMGB2/autophagy-regulatory loop has a critical role in MDR in GC. In addition, miR-23b-3p could be used as a prognostic factor for overall survival in GC. In conclusion, our data demonstrated that miR-23b-3p inhibited autophagy mediated by ATG12 and HMGB2 and sensitized GC cells to chemotherapy, and suggested the potential application of miR-23b-3p in drug resistance prediction and treatment.

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Authors
An, Y., Zhang, Z., Shang, Y., Jiang, X., Dong, J., Yu, P., Nie, Y., & Zhao, Q.
Affiliations
  • Ningbo University (CN)
  • Xijing Hospital (CN)
Corresponding author
  • Nie, Y
  • Zhao, Q
ORCID
Venue
Cell Death & Disease
Publisher
Springer Science and Business Media LLC
Published
2015-05-21
Volume
6
Issue
5
Pages
e1766-e1766
ISSN
2041-4889 (ISSN-L)
DOI
10.1038/cddis.2015.123
PMC
PMC4669702
OpenAlex
W338522219
Cited by
218
References
51
Citations by year
2026: 3 · 2025: 13 · 2024: 11 · 2023: 15 · 2022: 20 · 2021: 26 · 2020: 32 · 2019: 28 · 2018: 23 · 2017: 28 · 2016: 18 · 2015: 1
FWCI
7.72
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell Death and Disease (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
National Natural Science Foundation of China (81170432, 81430072, 81225003, 81370564, 81,227,901)
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 › Drug Transport and Resistance Mechanisms
Keywords
miR-23b-3p, gastric cancer, chemoresistance, multidrug resistance, ATG12, HMGB2, autophagy, microRNA target regulation, chemosensitization, prognostic factors, overall survival
MeSH terms
Autophagy-Related Protein 12, Antineoplastic Agents, Autophagy, Fluorouracil, Humans, Stomach, Stomach Neoplasms, Vincristine, Gene Expression Regulation, Neoplastic, Drug Resistance, Multiple, Drug Resistance, Neoplasm, HMGB2 Protein, Small Ubiquitin-Related Modifier Proteins, RNA Interference, RNA, Small Interfering, MicroRNAs, Cell Line, Tumor

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