iScience. 2026 Jun 11;29(7):116293. doi: 10.1016/j.isci.2026.116293. eCollection 2026 Jul 17.
ABSTRACT
Sulforaphane (SF) suppresses NSCLC metastasis by modulating miR-616-5p, which is transcriptionally upregulated by the oncogenic transcription factor SPI1. However, the roles of SF, SPI1, and miR-616-5p in NSCLC metastasis remain unclear. In this study, we found that SPI1 expression in NSCLC tissues positively correlated with miR-616-5p levels, and that SPI1 transcriptionally regulated miR-616-5p to promote NSCLC cell invasion and migration. Further analysis showed that SF directly binds SPI1, inhibiting its activity and downregulating miR-616-5p expression, thereby attenuating NSCLC metastasis. However, the poor stability of SF limits its clinical application. To address this, we developed a mesoporous silica nanoparticle (MSN)-based delivery system modified with hyaluronic acid and folic acid (MSNs@SF-HA-FA), which exhibited good stability, enhanced cellular uptake, and improved tumor targeting and anti-metastatic efficacy in NSCLC xenograft models. Collectively, our findings reveal the SPI1/miR-616-5p axis drives NSCLC metastasis and show that MSNs@SF-HA-FA enhances SF's anti-metastatic effect, highlighting its clinical potential.
PMID:42325568 | PMC:PMC13276326 | DOI:10.1016/j.isci.2026.116293