Research on the mechanism of exosomes from different sources influencing the progression of lung cancer

• Published in: Environmental toxicology Vol. 39; no. 8; pp. 4231 - 4248
• Main Authors: Mao, Guangxian, Liu, Jixian
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01.08.2024; Wiley Subscription Services, Inc
• Subjects: A549 Cells; Animals; Apoptosis; Bioinformatics; Cancer therapies; Cancer-Associated Fibroblasts - metabolism; CD8 antigen; CD8+T cells; Cell interactions; Cell Line, Tumor; Cell Proliferation; Cells; Disease Progression; Eukaryotic Initiation Factor-3 - genetics; Eukaryotic Initiation Factor-3 - metabolism; Exosomes; Exosomes - metabolism; Female; Forkhead Transcription Factors - genetics; Forkhead Transcription Factors - metabolism; Humans; In vivo methods and tests; Initiation factors; lncRNA‐FOXD3‐AS1; Lung cancer; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Lungs; Lymphocytes; Lymphocytes T; Male; Mice; Mice, Inbred BALB C; Mice, Nude; MicroRNAs - genetics; MicroRNAs - metabolism; miR‐2682; Neoplasms; Proteins; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; RNA-binding protein; RNA-Binding Proteins - genetics; RNA-Binding Proteins - metabolism; siRNA; Tumor cells; Tumors; tumor‐associated fibroblasts; lung cancer; CD8+T cells; tumor‐associated fibroblasts; miR‐2682; exosomes; lncRNA‐FOXD3‐AS1
• ISSN: 1520-4081; 1522-7278; 1522-7278
• DOI: 10.1002/tox.24292

As a key regulator of intercellular communication, exosomes are essential for tumor cells. In our study, we will explore the mechanisms of exosomes from different sources on lung cancer. We isolated CD8+T cells and cancer‐associated fibroblasts (CAFs) from venous blood and tumor tissues of lung cancer patients, and isolated exosomes. MiR‐2682 was high expression in CD8+T‐derived exosomes, and lncRNA‐FOXD3‐AS1 was upregulated in CAF‐derived exosomes. Online bioinformatics database analysis showed that RNA Binding Motif Protein 39 (RBM39) was identified as the target of miR‐2682, and eukaryotic translation initiation factors 3B (EIF3B) was identified as the RNA binding protein of FOXD3‐AS1. CD8+T‐derived exosomes inhibited the growth of A549 cells and promoted apoptosis, while miR‐2682 inhibits reversed these effects of CD8+T‐derived exosomes. CAF‐derived exosomes promoted the growth of A549 cells and inhibited apoptosis, while FOXD3‐AS1 siRNA reversed the effect of CAF‐derived exosomes. Mechanism studies have found that miR‐2682 inhibits the growth of lung cancer cells by inhibiting the expression of RBM39. FOXD3‐AS1 promoted the growth of lung cancer cells by binding to EIF3B. In vivo experiments showed that CD8+T cell‐derived exosome miR‐2682 inhibited lung cancer tumor formation, while CAF‐derived exosome FOXD3‐AS1 promoted lung cancer tumor formation. This study provides mechanistic insights into the role of miR‐2682 and FOXD3‐AS1 in lung cancer progression and provides new strategies for lung cancer treatment.