Cancer cell-derived extracellular vesicles (EVs) have extensive application in the formation of their environment, including
metastasis. This study explored the ability of
gastric cancer (GC) cell-derived EVs-mediated
microRNA-129-5p/
E2F transcription factor 7/
mitogen-activated protein kinase/extracellular regulated
protein kinase (miR-129-5p/E2F7/MAPK/ERK) axis to affect the peritoneal
metastasis of GC by delivering
lncRNA small nucleolar RNA host gene 12 (SNHG12). EV-derived
lncRNA and SNHG12/miR-129-5p/E2F7 network were determined by bioinformatics analysis. The regulatory relationship among SNHG12, miR-129-5p, and E2F7 was verified using a combination of dual-
luciferase reporter gene,
RNA immunoprecipitation, and
RNA pull-down assays. The SNHG12, miR-129-5p, and E2F7 expression was measured by RT-qPCR. After GC cell-derived EVs were isolated and co-cultured with human peritoneal mesothelial cells (HPMCs), the uptake of EVs by HPMCs was observed under
laser scanning confocal microscopy. Cell viability and apoptosis were examined using cell counting kit-8 and flow cytometry, respectively. Western blot analysis was performed to measure the mesothelial-mesenchymal transition (
MMT)-related
protein expression. The pathological and morphological characteristics of metastatic
tumors in nude mice were observed by
hematoxylin-
eosin staining. A high SNHG12 expression was correlated with the poor prognosis of patients with GC. GC-derived EVs led to increased HPMC apoptosis and
MMT by transferring SNHG12, whereas the knockdown of SNHG12 annulled the aforementioned results. SNHG12 sponged miR-129-5p to boost E2F7 expression and activate the MAPK/ERK signaling, thus inducing HPMC apoptosis and
MMT. In vivo experiments further verified that EVs derived from GC cells promoted peritoneal
metastasis in nude mice. GC cell-derived EVs elevated the E2F7 expression and activated the MAPK/ERK signaling to promote peritoneal
metastasis through the delivery of SNHG12.