Association study of hsa_circ_0001946, hsa-miR-7-5p and PARP1 in coronary atherosclerotic heart disease

Background: Our previous work identified an aberrant expression of hsa_circ_0001946 in coronary atherosclerotic heart disease (CHD). Here we aimed to verify the role of hsa_circ_0001946 as a biomarker for CHD, and explore the clues of its downstream regulation. Methods: The hsa_circ_0001946 expression in CHD patients (n = 120) and controls (n = 120) were confirmed with qRT-PCR. CircBank and miRDB were used for target analysis in silico. Spearman correlation test was performed to infer potential interrelationships among the nucleic acid molecular biomarkers, and their predictive abilities were examined using receiver operating characteristic (ROC) curves. Results: Hsa_circ_0001946 was validated to be significantly up-regulated in the peripheral blood mononuclear cells of CHD patients, and revealed as an independent indicator of increased CHD risk (odds ratio: 2.364; 95% confidence interval [CI]: 1.765-3.165) after adjusting for confounding factors. Hsa-miR-7-5p was found to own the largest number of binding sites in has_circ_0001946 sequence, and among its targets predicted, the poly ADP ribose polymerase 1 (PARP1) has been implicated in the pathophysiology of CHD. Spearman analysis indicated negative correlations of hsa-miR-7-5p with hsa_circ_0001946 and PARP1, respectively; while hsa_circ_0001946 was positively correlated with PARP1. The prediction accuracy of hsa_circ_0001946 in CHD was evaluated, showing an area under the ROC curve of 0.897 (95% CI: 0.791-0.961), which could further increase to 0.957 (95% CI: 0.870-0.992) upon a combination of hsa-miR-7-5p and PARP1. Conclusion: The present work demonstrated the predictive power of hsa_circ_0001946, hsa-miR-7-5p and PARP1 as combined biomarkers for CHD, and suggests a regulatory axis they consisted might contribute to the CHD development. (c) 2020 Elsevier B.V. All rights reserved.

Automated summary

The study confirmed the up-regulation of hsa_circ_0001946 in CHD patients, serving as an independent indicator of increased CHD risk. Hsa-miR-7-5p was identified as a potential target with the largest number of binding sites in hsa_circ_0001946, while PARP1 has implications in the pathophysiology of CHD. The predictive accuracy of hsa_circ_0001946 in CHD was evaluated, which could be further enhanced when combined with hsa-miR-7-5p and PARP1.