Circular RNAs (circRNA) result from pre-mRNA back-splicing. Next generation sequencing has a blind spot for these circRNAs due to their lack of polyA tails and thus their abundance has only recently been appreciated. Using appropriate primers and/or RNase A enrichment, over 10,000 circRNAs have now been identified in multicellular animals and plants.
These circRNAs have several proposed functions including regulation of RNA splicing, auto-regulation of gene transcription, acting as micro[mi]RNA sponges, protein sponges, generate translation products, drive genome evolution through reverse transcription and integration. They may also serve as biomarkers of disease. There has been little direct study of circRNAs and their possible regulation of miRNA in acute coronary syndrome (ACS).
Guoan Zhao of the Henan Engineering Research Center for Clinical Data and Biobank of Cardiovascular Diseases, China, and colleagues, sought to address this by screening circRNA and miRNA expression profiles in peripheral blood of ACS patients by microarray. Possible circRNA-miRNA interactions were predicted. The results were published in the journal of Evidence-Based Complementary and Alternative Medicine.
Of the circRNA assessed, 121 were upregulated and 145 downregulated in the disease state. By contrast only 3 miRNAs were found to be differentially regulated. Extensive interactions between circRNA and miRNA were predicted.
One miRNA was predicted to bind over 300 different circRNAs, however a range of 1-20 was more typical. Conversely, 1 circRNA could also bind over 100 different miRNA. Interestingly, the control group appeared to contain more “hyper-targeted” miRNA, than the disease groups, perhaps indicating a protective effect of circRNA.
The functional consequences of the miRNA and circRNA interactions were not investigated and could be important. The other potential targets of circRNAs, such as proteins, were not considered or predicted.
“In conclusion, circRNAs are involved in the occurrence and development of ACS through multiple points of network correlation for miRNA regulation. We speculate that circRNAs may serve as a potential therapeutic avenue for a pathophysiological mechanism of ACS and may even become diagnostic and therapeutic biomarkers for ACS. In the future, we will perform in vitro and in vivo tests to further validate the involvement of circRNAs in the atherosclerotic process of ACS,” stated the authors.