CircSMARCC1 and CircLRBA are potential biomarkers in forensic postmortem diagnosis of acute myocardial infarction

Abstract

Postmortem diagnosis of acute myocardial infarction (AMI), especially early AMI, is a challenge for forensic scientists. Circular RNAs (circRNA) are a unique type of RNA with a closed loop structure and more stability, compared with linear RNA. We aimed at evaluating whether circRNAs are ideal postmortem diagnostic markers for AMI. We employed bioinformatics methods to screen for target circRNAs. Divergent and convergent primers were used to confirm the loop structure. Ribonuclease R (RNaseR) digestion and artificial simulated room temperature test were performed to evaluate the stability of circRNAs. Furthermore, RT-PCR analysis was performed to assess the expressions of target circRNAs in a mouse model of AMI and in autopsy cases, while the diagnostic significance of circRNAs was evaluated by the receiver-operator characteristic (ROC) curve. The bioinformatics analysis screened out circSMARCC1 and circLRBA as target circRNAs. Agarose gel electrophoresis revealed the loop structure of target circRNAs. RNaseR digestion and the artificial simulated room temperature test showed that the stability of circRNAs was good. In mouse AMI model, circSMARCC1 levels were elevated while circLRBA levels were suppressed. Finally, in forensic autopsy cases, circSMARCC1 levels were significantly elevated, while circLRBA levels were significantly suppressed in the MI and early-MI group, relative to the normal control group. The ROC curve analysis showed that both circSMARCC1 and circLRBA can distinguish between AMI and normal control cases. Futher, a combination of the two circRNAs can increase the diagnostic efficacy of AMI. Thus, circSMARCC1 and circLRBA are potential biomarkers for postmortem diagnosis of AMI.