Gastric cancer cell-derived exosomes can regulate the biological functions of mesenchymal stem cells by inducing the expression of circular RNA circ_0004303.

As an important component of the dynamic tumor microenvironment, mesenchymal stem cells (MSCs) can interact with tumor cells to promote tumor growth. Treatment with tumor cell-derived exosomes can change the biological functions of MSCs. We want to study the mechanism by which exosomes derived from gastric cancer cells affect the biological functions of MSCs. After MSCs were treated with AGS cell-derived exosomes, circular RNAs differentially expressed in MSCs were verified using existing RNA microarray results combined with real-time quantitative polymerase chain reaction (qRT-PCR). Then, circular RNAs were knocked down or overexpressed by plasmids, and the functions of circular RNAs were evaluated by Migration and invasion assay. Dual luciferase reporter assay was used to evaluate the potential mechanism of circular RNAs. After treatment with exosomes secreted by AGS, the results showed that some circular RNAs expressed by human adipose derived mesenchymal stem cells showed significant differences. The elevated circ_0004303 promoted the migration and invasion of human adipose derived mesenchymal stem cells in vitro. Circ_0004303 upregulated the expression of ALCAM by acting as a miR-148a-3p sponge, thereby enhancing the migration and invasion functions of human adipose derived mesenchymal stem cells. Therefore, exosomes secreted by AGS can affect the expression of circular RNAs in human adipose derived mesenchymal stem cells. Hsa_circ_0004303 can regulate the migration and invasion of human adipose derived mesenchymal stem cells via the miR-148a-3P /ALCAM axis. This study suggests that tumor cells can promote the migration and homing of MSCs in adjacent tissues by secreting exosomes.