7SK-enriched exosomes suppress the cancer phenotypes in human lung cancer cells: insights from 2D and microfluidic 3D in vitro models

Lung cancer, being the top cause of global cancer-related mortality, calls for effective treatments. RN7SK (7SK) is a long non-coding RNA (lncRNA) that plays a significant role in the regulation of gene transcription and thereby controls essential cellular activities. Limited evidence supports the anticancer potential of 7SK, and its suppressive effects have not been tested against lung cancer. This study explored the anticancer effects of RN7SK (7SK), a long non-coding RNA known to regulate gene transcription, through exosome-mediated delivery in lung cancer cells. Treatment with exosome-loaded 7SK (Exo-7SK) significantly elevated 7SK levels in non-small-cell lung cancer cells and suppressed key cancer traits. Exo-7SK reduced cell viability and proliferation, promoted apoptosis, and inhibited migration and invasion by shifting gene expression away from epithelial-mesenchymal transition. It also impaired spheroid formation and reduced spheroid dispersion and viability in 3D microfluidic cultures. In conclusion, our findings highlight the cancer-suppressive potential of exosome-mediated 7SK delivery against lung cancer, demonstrating significant efficacy in both 2D and 3D culture models. These observations warrant further confirmation in future studies employing advanced designs and clinically relevant models.