Background
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).
Conclusion
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.
Methods
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 (IC50) 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.
Results
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 in vivo.