3088 - Bystander Effect of Exosomal miR-3065-5p Inhibits Lung Cancer Cells by Suppressing Radiation-Induced Profilin 2

05:00pm - 06:00pm PT

Hall F

Screen: 8

POSTER

Presenter(s)

Jaeha Lee, MD, PhD - Asan Medical Center, Seoul 138-736, Seoul

J. Ryu¹, J. Lee², J. Lee³, and S. W. Lee³; ¹Department of Convergence Medicine, Asan Medical Center, Seoul, Korea, Republic of (South), ²La Sierra University, Riverside, CA, ³Department of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea, Republic of (South)

Purpose/Objective(s):

Recent observations suggest that exosomes may act as negative effectors in radiotherapy. Radiation suppresses exosomal miR-3065-5p, which regulates profilin 2 (PFN2) targeting. This suppression leads to the upregulation of PFN2, potentially contributing to radioresistance in tumor cells.

Materials/Methods:

Through omics analysis of WI38 and A549 cells exposed to 2 Gy of radiation, we identified miR-3065-5p as a microRNA targeting PFN2. The roles of exosomal miR-3065-5p and PFN2 were examined using cell viability assays, wound healing assays, and transmigration assays, validated in the xenograft model.

Results:

After accounting for baseline expression changes in WI38 cells, PFN2 protein levels were significantly upregulated in A549 cells exposed to 2 Gy of radiation. Additionally, exosomes derived from irradiated A549 cells found to contain miR-3065-5p, which regulates PFN2 expression. H1299 or A549 cells overexpressing PFN2 exhibited enhanced growth, whereas EKVX cells, which have low PFN2 expression, demonstrated markedly slower growth. Radiation-induced exosomes contained higher levels of PFN2 protein compared to that in controls. Treating EKVX and human aortic endothelial cells (hECs) with these exosomes increased PFN2 expression in both cell types. Additionally, radiation-induced exosomes upregulated angiogenesis-related genes in hECs, and EKVX cells gained the ability to transmigrate into hECs and proliferate. Importantly, the metastatic abilities of EKVX cells stimulated by radiation-induced exosomes were significantly reduced pretreatment with miR-3065-5p mimic. In the xenograft model, injection of the miR-3065-5p mimic notably decreased tumor volume, Ki-67 expression, and angiogenesis.

Conclusion: miR-3065-5p, present in radiation-induced exosomes, reduces lung adenocarcinoma cell proliferation, migration, and invasion by suppressing PFN2 expression.