ArticlePloS one2014
Alteration in Mir-21/PTEN expression modulates gefitinib resistance in non-small cell lung cancer.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers, 1 of them a synthesis that pooled it.
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Who cites it
67 citing papers in PubMed, 1 synthesis or guideline pooled it, 116 citations in OpenAlex.
- PTEN expression is a prognostic marker for patients with non-small cell lung cancer: a systematic review and meta-analysis of the literature.Oncotarget · 2016Pooled it
- The Role and Therapeutic Potential of Non-coding RNAs in Resistance to EGFR - TKIs Targeted Therapy for Non-small Cell Lung Cancer.Current medicinal chemistry · 2025Review
- Molecular roles of microRNA-21 and exosomal miR-21 in gastrointestinal cancers: diagnostic, therapeutic, and drug resistance insights.Frontiers in molecular biosciences · 2025Review
- Review
- Targeting EGFR with molecular degraders as a promising strategy to overcome resistance to EGFR inhibitors.Future medicinal chemistry · 2024Review
- Composition of Conditioned Media from Radioresistant and Chemoresistant Cancer Cells Reveals miRNA and Other Secretory Factors Implicated in the Development of Resistance.International journal of molecular sciences · 2023Review
- MicroRNA in lung cancer-a novel potential way for early diagnosis and therapy.Journal of applied genetics · 2023Review
- ZDHHC2-Mediated AGK Palmitoylation Activates AKT-mTOR Signaling to Reduce Sunitinib Sensitivity in Renal Cell Carcinoma.Cancer research · 2023Article
- MicroRNA-21 guide and passenger strand regulation of adenylosuccinate lyase-mediated purine metabolism promotes transition to an EGFR-TKI-tolerant persister state.Cancer gene therapy · 2022Article
- MicroRNAs and Drug Resistance in Non-Small Cell Lung Cancer: Where Are We Now and Where Are We Going.Cancers · 2022Review
- Regulatory network identified by pulmonary transcriptome and proteome profiling reveals extensive change of tumor-related genes in microRNA-21 knockout mice.Journal of cancer research and clinical oncology · 2022Article
- Emerging strategies to overcome resistance to third-generation EGFR inhibitors.Journal of hematology & oncology · 2022Review
- MiRNAs in Lung Cancer: Diagnostic, Prognostic, and Therapeutic Potential.Diagnostics (Basel, Switzerland) · 2022Review
- Functions of non-coding RNAs in regulating cancer drug targets.Acta biochimica et biophysica Sinica · 2022Review
- Molecular Beacon for Detection miRNA-21 as a Biomarker of Lung Cancer.International journal of molecular sciences · 2022Article
- Review
- lncRNA NBAT1 Inhibits Cell Metastasis and Promotes Apoptosis in Endometrial Cancer by Sponging miR-21-5p to Regulate PTEN.Computational and mathematical methods in medicine · 2022Article
- Identification of microRNAs that promote erlotinib resistance in non-small cell lung cancer.Biochemical pharmacology · 2021Article
- Association between miRNA signatures in serum samples from epidermal growth factor inhibitor treated patients and skin toxicity.Oncotarget · 2021Article
- Chemotherapeutic drugs: Cell death- and resistance-related signaling pathways. Are they really as smart as the tumor cells?Translational oncology · 2021Review
7 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Resistance to TKI treatment is a major obstacle in effective treatment of NSCLC. Besides EGFR mutation status, the mechanisms involved are largely unknown. Some evidence supports a role for microRNA 21 in modulating drug sensitivity of chemotherapy but its role in NSCLC TKI resistance still remains unexplored. This study aimed to investigate whether NSCLC miR-21 mediated resistance to TKIs also results from Pten targeting. Here, we show miR-21 promotes cancer by negatively regulating Pten expression in human NSCLC tissues: high miR-21 expression levels were associated with shorter DFS in 47 NSCLC patients; high miR-21/low Pten expression levels indicated a poor TKI clinical response and shorter overall survival in another 46 NSCLC patients undergoing TKI treatment. In vitro assays showed that miR-21 was up-regulated concomitantly to down-regulation of Pten in pc-9/GR cells in comparison with pc-9 cells. Moreover, over-expression of miR-21 significantly decreased gefitinib sensitivity by down-regulating Pten expression and activating Akt and ERK pathways in pc-9 cells, while miR-21 knockdown dramatically restored gefitinib sensitivity of pc-9/GR cells by up-regulation of Pten expression and inactivation of AKT and ERK pathways, in vivo and in vitro. We propose alteration of miR-21/Pten expression as a novel mechanism for TKI resistance in NSCLC cancer. Our findings provide a new basis for using miR 21/Pten-based therapeutic strategies to reverse gefitinib resistance in NSCLC.
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