EV-transferred miR-7111-3p inhibits malignant phenotypes and tumor growth in nasopharyngeal carcinoma via targeting APP-regulated epithelial-mesenchymal transition.

background and purposeExtracellular vesicle (EV)-mediated transfer of microRNAs has emerged as a critical mechanism driving tumor progression, yet its functional relevance in nasopharyngeal carcinoma (NPC) remains poorly defined. This study sought to elucidate the functional role and molecular mechanism of EV-associated miR-7111-3p in NPC progression.

methodsmiR-7111-3p expression was measured in serum samples from NPC patients and in NPC cell lines. Functional effects were evaluated through gain- and loss-of-function assays in vitro and in xenograft models. Direct targeting of amyloid precursor protein (APP) by miR-7111-3p was validated using dual-luciferase reporter assays. EV-mediated transfer was assessed by EV isolation, characterization, and co-culture experiments.

resultsmiR-7111-3p was significantly downregulated in NPC serum and cell lines. Its overexpression markedly suppressed NPC cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT), whereas its knockdown exerted the opposite effects. APP was identified as a direct target of miR-7111-3p, and APP overexpression reversed the inhibitory effects induced by miR-7111-3p. EVs derived from miR-7111-3p-deficient NPC cells promoted APP expression, proliferation and migration in recipient NP69 cells, whereas inhibition of EV secretion attenuated these effects. In vivo, miR-7111-3p overexpression reduced xenograft tumor growth and downregulated APP expression.

conclusionThese findings identify a novel EV-miR-7111-3p-APP signaling axis that regulates EMT, malignant phenotypes and tumor growth in NPC, highlighting its potential as a therapeutic target.