miR-206-loaded albumin nanoparticles suppress ovarian cancer cells by inhibiting c-met oncogenic pathway

Abstract

Ovarian cancer is one of the most lethal gynecological malignancies, often diagnosed at advanced stages with poor survival outcomes. Despite improvements in surgery and chemotherapy, resistance to conventional therapies remains a major obstacle, underscoring the urgent need for novel and biocompatible therapeutic strategies. MicroRNA-206 (miR-206) functions as a potent tumor suppressor by targeting the c-Met/PI3K/AKT/mTOR signaling pathway; however, its therapeutic application is limited by instability, enzymatic degradation, and inefficient cellular uptake. We therefore hypothesized that bovine serum albumin nanoparticles (BSA-NPs) could serve as an effective and safe carrier for miR-206, enhancing its intracellular delivery and restoring tumor-suppressive activity in ovarian cancer cells. Consistent with this rationale, the nanocarriers exhibited favorable morphology, biocompatibility, and efficient cellular uptake, leading to elevated intracellular miR-206 levels. Functional assays demonstrated that BSA-NPs loaded with miR-206 inhibited proliferation, migration, and invasion while inducing apoptosis in SKOV-3 cells. Gene and protein analyses further confirmed suppression of c-Met/AKT/mTOR signaling, downregulation of oncogenic and anti-apoptotic markers, and restoration of tumor-suppressive regulators. These findings highlight BSA-NPs as a promising preclinical platform for miR-206 delivery, capable of reactivating tumor-suppressive pathways in vitro, and provide a strong rationale for further validation across additional models to overcome key barriers in the clinical translation of miRNA-based therapeutics for ovarian cancer.