Exosome-Derived Circ-PVT1 Contributes to Cisplatin Resistance by Regulating Autophagy, Invasion, and Apoptosis Via miR-30a-5p/YAP1 Axis in Gastric Cancer Cells.

Emerging studies manifested that exosomal RNAs had pivotal roles in human cancer therapies. This article aimed to research the regulatory mechanism of exosomal circRNA-plasmacytoma variant translocation 1 (circ-PVT1) in cisplatin (DDP) resistance of gastric cancer (GC). Exosomes were isolated by ExoQuick method and ultracentrifugation and then identified through transmission electron microscope and the examination of exosome markers. Related proteins were detected using Western blot. Quantitative real-time polymerase chain reaction (qRT-PCR) was applied for measuring circ-PVT1, microRNA-30a-5p (miR-30a-5p), and Yes-associated protein 1 (YAP1) expression. The half inhibitory concentration (IC) of DDP was assessed by 3-(4, 5-dimethylthiazol-2-y1)-2, 5-diphenyl tetrazolium bromide (MTT). Cell apoptosis and invasion were, respectively, determined using flow cytometry and transwell assay. Target relationship was confirmed by dual-luciferase reporter assay. The impact of circ-PVT1 on DDP resistance was explored via xenograft tumor assay. Exosomal circ-PVT1 was upregulated while miR-30a-5p was downregulated in DDP-resistant GC serums and cells. Circ-PVT1 knockdown repressed DDP resistance in DDP-resistant GC cells via promoting apoptosis and decreasing invasion or autophagy by negatively targeting miR-30a-5p. YAP1 was a direct target of miR-30a-5p. MiR-30a-5p overexpression inhibited DDP resistance via reducing YAP1. Circ-PVT1 modulated YAP1 expression by targeting miR-30a-5p. Circ-PVT1 depression expedited DDP sensitivity of GC via miR-30a-5p/YAP1 axis . Exosomal circ-PVT1 facilitated DDP resistance via modulating autophagy, invasion and apoptosis by miR-30a-5p/YAP1 axis in GC cells. Exosomal circ-PVT1 might be a prospective indicator in DDP therapy of GC.