Exosomal miR-106a derived from gastric cancer promotes peritoneal metastasis via direct regulation of Smad7

摘要

Peritoneal metastasis develops in more than half of patients with gastric cancer but influencing factors are poorly characterized. Exosomes are increasingly recognized as a new mediator in cancer directional metastasis through the transfer of nucleic acids or proteins to neighboring or distant cells. The role of exosomes in peritoneal metastasis and whether it could establish pre-metastatic milieu are largely unknown. Here, we assessed the migration of gastric cancer (GC) cells and identified that PKH26-labeled exosomes from GC cells can be ingested by peritoneal mesothelial cells (MCs). Additionally, miRNA (miR-106a) that highly enriched in GC-derived exosomes (GC-exos) and essential for destroying the mesothelial barrier was demonstrated through the observation of the injury of the MCs including migratory enhancement and imbalance of apoptosis and proliferation. Moreover, either stimulating miR-106a or treatment with GC-exos could inhibit the expression of Smad7, accompanied by the concurrent elevated α-SMA and fibronectin in MCs. Silencing of miR-106a abolished GC-exos-induced gene expression in MCs. The MCs regain the viability, apoptosis reduction and Smad7 expression after rescue experiment conducted in miR-106a-enriched GC-exos. Xenograft model suggested that exosomal miR-106a had a potential to promote tumor growth through targeting Smad7. Collectively, we revealed that the delivery of miR-106a from GC-exos plays a crucial role in gastric cancer peritoneal metastasis.