2.3 circRNAs and atherosclerosis
CircRNAs are closed circular molecules, which distinguishes them from other linear RNA molecules. CircRNAs were originally considered as by-products of mRNA cleavage, but now it is thought to be stable and functionally ncRNAs (L. L. Chen, 2016). Compared to miRNAs, circRNAs are less studied ncRNAs in atherosclerosis. Still, there are studies that have shown circRNAs can regulate the fate and function of atherosclerosis-associated cells, including endothelial cells, macrophages, and VSMCs. As with lncRNAs, circRNAs can also compete with miRNAs as ceRNAs, which is the mostly investigated mechanisms (Ren et al., 2021). In endothelial cells, a study demonstrated that circ-RELL1 plays a pro-inflammatory role in endothelial cells by directly binding to miR-6873-3p and subsequently activating NF-κB signaling pathway (H. S. Huang, Huang, Yu, Xue, & Zhu, 2020). Circ_0086296 induces aberrant endothelial cell phenotypes by spongesizing miR-576-3p, resulting in severe atherosclerotic lesions (M. Zhang et al., 2022). In VSMCs, circRNA-0044073 promotes the proliferation and invasion of VSMCs by targeting miR-107 and activating the JAK/STAT signaling pathway (L. Shen et al., 2019). In macrophages, overexpression of circ_0004104 results in dysregulation of atherosclerosis-related genes in THP-1-derived macrophages (L. Wang et al., 2019). It is noticed that the role of circRNAs in atherosclerosis has rarely been studied, which may become a research hotspot in the future.
Since the role of ncRNAs in atherosclerosis is emerging, they have been considered as potential drug targets in developing therapeutic agents. As we know, traditional Chinese medicine has a long history of treating atherosclerosis in China. In particular, studies have shown that the monomers extracted from traditional Chinese medicine are the main functional components that possess anti-atherosclerotic activity, and these activities can be mediated by ncRNAs.