circROCK1 Promotes septic myocardial injury through regulating miR-96-5p/OXSR1 axis

Objective: A recent high-throughput sequencing showed that circular RNA Rho-associated kinase 1 (cir-cROCK1) is abnormally highly expressed in sepsis, but whether it is involved in sepsis development remains unclear. The objective of this study was to investigate the biological function of circROCK1 in sepsis-induced myocardial injury and reveal its potential downstream molecular mechanism.Methods: Real-time reverse transcriptase-polymerase chain reaction was applied to detect circROCK1 and miR-96-5p expressions in the serum of septic patients. Spearman correlation analysis examined the correlation between circROCK1 and the clinicopathological characteristics of septic patients. The Cecal puncture and ligation (CLP) method was used to establish an in vivo sepsis model. circROCK1 and miR-96-5p expressions in mice were modified by injection of lentivirus or oligonucleotide. The left ventricular systolic pressure, left ventricular end-diastolic pressure, and the maximum increase/decrease rate of left ven-tricular pressure were checked. ELISA was applied to detect inflammatory factors levels as well as myocardial injury markers levels. Hematoxylin and eosin staining was performed to observe pathological changes in my-ocardial tissues, and Western blot examined phospho-rylated nuclear factor (NF)-kappa B and oxidative stress-re-sponsive 1 (OXSR1) expression. Dual luciferase reporter experiment was conducted to confirm the targeting re-lationship between circROCK1, OXSR1, and miR-96-5p. Results: circROCK1 and OXSR1 were highly expressed in sepsis and miR-96-5p was under-expressed. circROCK1 was positively correlated with serum creatinine, C-reactive protein, procalcitonin, and sequential organ failure assessment scores in septic patients. Silencing circROCK1 could improve the diastolic and systolic function of CLP mice, as well as myocardial damage, reduce myocardial tissue edema and necrosis, and in-hibit inflammatory factor level and phosphorylated NF-kappa B expression. Down-regulating miR-96-5p promoted myocardial injury in CLP mice. Silencing circROCK1 and miR-96-5p inhibited and promoted OXSR1 expression, respectively. Both circROCK1 and OXSR1 had a target -ing relationship with miR96-5p.Conclusion: CircROCK1 promotes myocardial injury in septic mice by regulat-ing the miR-96-5p/OXSR1 axis, and it can be used as a potential target for treating septic myocardial dysfunc-tion.