AI Article Synopsis
- Overcoming resistance to osimertinib, an important drug for lung cancer, hinges on understanding the role of EV-derived microRNAs (EV-miRNAs) in treatment outcomes.
- Researchers found that the microRNA miR-130a-3p was upregulated in EVs from osimertinib-resistant lung adenocarcinoma cells, promoting cell survival against the drug.
- Lower levels of serum miR-130a-3p in patients were linked to better treatment progression, suggesting it could be a valuable biomarker and therapeutic target for managing osimertinib resistance.
Article Abstract
Overcoming resistance to epidermal growth factor receptor tyrosine kinase inhibitors, including osimertinib, is urgent to improve lung cancer treatment outcomes. Extracellular vesicle (EV)-derived microRNAs (EV-miRNAs) play important roles in drug resistance and serve as promising biomarkers. In this study, we aimed to identify EV-miRNAs associated with osimertinib resistance and investigate their clinical relevance. The release of excess EVs was confirmed in the osimertinib-resistant lung adenocarcinoma cell line PC9OR. The exposure of PC9OR-derived EVs and EV-miRNAs to PC9 cells increased cell viability after osimertinib treatment. Microarray analysis revealed that miR-130a-3p was upregulated in EVs derived from PC9OR cells and another osimertinib-resistant cell line (H1975OR). Transfection with miR-130a-3p attenuated osimertinib-induced cytotoxicity and apoptosis in both PC9 and H1975 cells, whereas osimertinib resistance in PC9OR cells was reversed after miR-130a-3p inhibition. Bioinformatics analysis revealed that runt-related transcription factor 3 is a target gene of miR-130a-3p, and it induced osimertinib resistance in PC9 cells. Patients with lower baseline serum miR-130a-3p concentrations had longer progression-free survival. miR-130a-3p is a potential therapeutic target and a predictive biomarker of osimertinib resistance in adenocarcinomas.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11489462 | PMC |
| http://dx.doi.org/10.1038/s41598-024-76196-1 | DOI Listing |
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