Circular RNA rno-circ_016033 regulates diabetic atherosclerosis progression via sponging rno-miR-336-3p

The objective of this study was to examine the role of circular RNAs (circRNAs) in rats with diabetic atherosclerosis. Atherosclerosis model of diabetic rats were established to observe the behavior, serum biochemical indicators, arterial structure and fat accumulation of rats. High-throughput sequencing was employed to identify differentially expressed circRNAs and mRNAs. CircRNAs (rno-circ_011730, rno-circ_004411, and rno-circ_016033) expression in control and diabetic atherosclerosis tissues were verified. In vitro cell experiments were performed to investigate the regulatory mechanism involving the rno-circ_016033/rno-miR-336-3p/Fas axis. Finally, we knocked down rno-miR-336-3p for rescue experiments. Through in vivo verification, we found the atherosclerosis model of diabetic rats was successfully established. In rats with diabetic atherosclerosis, there were 23 up-regulated circRNAs, 21 down-regulated circRNAs, 779 up-regulated mRNAs, and 531 down-regulated mRNAs. In vivo validation experiments showed that rno-circ_016033 and Fas expressions in AS group were significantly elevated than NC group. Further in vitro cell experiments showed that rno-circ_016033 regulated macrophage function to participate in diabetic atherosclerosis. Additionally, dual-luciferase assay confirmed that rno-circ_016033 adsorbed rno-miR-336-3p and rno-miR-336-3p targeted the 3'UTR of Fas. Finally, knocking down rno-miR-336-3p reversed changes in macrophage function caused by interference with rno-circ_016033 in vitro. Together, rno-circ_016033/rno-miR-336-3p/Fas axis was involved in diabetic atherosclerosis.