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Updated: Dec 22, 2025

Exosomal miRNA Analysis in Non-small Cell Lung Cancer NSCLC Patients' Plasma Through qPCR: A Feasible Liquid Biopsy Tool
Published on: May 27, 2016
Exosomal long non-coding RNA MSTRG.292666.16 is associated with osimertinib (AZD9291) resistance in non-small cell
Qinfang Deng1, Qiyu Fang1, Boxiong Xie2
1Department of Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
Abstract:
Acquired resistance of osimertinib is encountered in clinic treatment of non-small cell lung cancer (NSCLC). However, the molecular mechanisms of osimertinib resistance are not fully revealed. This study aimed to investigate the roles of exosomes in delivering osimertinib resistance in NSCLC. Exosomes were successfully isolated. LncRNA sequencing identified a total of 123 differentially expressed lncRNAs, including 45 upregulated lncRNAs and 78 downregulated lncRNAs. The relative expression level of lncRNA MSTRG.292666.16 was significantly upregulated in osimertinib-resistant plasma, osimertinib-resistant H1975R cells and their derived exosomes, compared with those in osimertinib- sensitive plasma, H1975 cells and exosomes (P < 0.05). Besides, osimertinib-resistant exosomes could regulate gene expressions induced by osimertinib, including miRNA-21, miRNA-125b, TGFβ, ARF6 and c-Kit. Osimertinib-resistant exosomes could be taken up by osimertinib-sensitive H1975 cells and resulting in osimertinib-resistance in vivo. Knockdown of lncRNA MSTRG.292666.16 decreased osimertinib resistance of H1975R cells. Our results suggest that exosomal lncRNA MSTRG.292666.16 might be associated with osimertinib resistance in NSCLC.
Insights
Exosomes play a role in osimertinib resistance in non-small cell lung cancer (NSCLC). Exosomal lncRNA MSTRG.292666.16 was found to be upregulated and contribute to this resistance.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Acquired resistance to osimertinib is a significant clinical challenge in non-small cell lung cancer (NSCLC) treatment.
- The precise molecular mechanisms underlying osimertinib resistance remain incompletely understood.
Purpose of the Study:
- To investigate the role of exosomes in mediating osimertinib resistance in NSCLC.
- To identify specific molecular players, such as long non-coding RNAs (lncRNAs), involved in exosome-mediated resistance.
Main Methods:
- Isolation and characterization of exosomes from NSCLC cells and plasma.
- LncRNA sequencing to identify differentially expressed lncRNAs between sensitive and resistant samples.
- Functional studies involving exosome uptake, gene expression analysis, and knockdown experiments.
Main Results:
- LncRNA sequencing identified 123 differentially expressed lncRNAs.
- LncRNA MSTRG.292666.16 was significantly upregulated in osimertinib-resistant cells, plasma, and their derived exosomes.
- Osimertinib-resistant exosomes were taken up by sensitive cells, inducing resistance and altering gene expression (miRNA-21, miRNA-125b, TGFβ, ARF6, c-Kit).
- Knockdown of lncRNA MSTRG.292666.16 reduced osimertinib resistance in H1975R cells.
Conclusions:
- Exosomal lncRNA MSTRG.292666.16 is implicated in the development of osimertinib resistance in NSCLC.
- This lncRNA may serve as a potential therapeutic target or biomarker for overcoming treatment resistance.
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