Exosomal circ_0091741 promotes gastric cancer cell autophagy and chemoresistance via the miR-330-3p/TRIM14/Dvl2/Wnt/β-catenin axis.

Abstract

The importance of cancer cell-released exosomes in the treatment of various cancers has been well-characterized. The current study aims to examine the potential biological functions of gastric cancer (GC) cell-released exosomes delivering a novel circRNA circ_0091741 in GC and the underlying molecular mechanism. Expression of circ_0091741 was examined in the GC cells, (OXA)-resistant HGC-27 (HGC-27/OXA) cells, and isolated exosomes, after which its downstream miRNA was analyzed. The role and mechanism of the circ_0091741 transmitted by GC cells-derived exosomes in GC cell autophagy and chemoresistance were assessed using various molecular biological methods. A mouse tumor xenograft model was prepared to discern the effect of circ_0091741 on tumorigenesis in vivo. GC cells and their exosomes were characterized by upregulated circ_0091741 expression. circ_0091741 transferred by GC cell-derived exosomes induced the autophagy and OXA resistance of GC cells. circ_0091741 obstructed the binding of miR-330-3p to TRIM14 and increased the expression of TRIM14. TRIM14 could cause activation of the Wnt/β-catenin signaling pathway by stabilizing Dvl2. By this mechanism, the autophagy and OXA resistance of GC cells were augmented. In vivo assay unfolded that orthotopic implantation of exosomal circ_0091741 overexpressed GC cells into nude mice enhanced tumorigenesis. In conclusion, our study emphasized the promotive role of exosomal circ_0091741 in autophagy and chemoresistance of GC cells, thus laying the basis for the development of novel therapeutic targets for GC treatment.