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.