Role of Circular RNAs in Atherosclerosis through Regulation of Inflammation, Cell Proliferation, Migration, and Apoptosis: Focus on Atherosclerotic Cerebrovascular Disease

Abstract

Atherosclerosis (AS) is a disease dangerous to human health and the main pathological cause of ischemic cardiovascular diseases. Although its pathogenesis is not fully understood, numerous basic and clinical studies have shown that AS is a chronic inflammatory disease existing in all stages of atherogenesis. It may be a common link or pathway in the pathogenesis of multiple atherogenic factors. Inflammation is associated with AS complications, such as plaque rupture and ischemic cerebral infarction. In addition to inflammation, apoptosis plays an important role in AS. Apoptosis is a type of programmed cell death, and different apoptotic cells have different or even opposite roles in the process of AS. Unlike linear RNA, circular RNA (circRNA) a covalently closed circular non-coding RNA, is stable and can sponge miRNA, which can affect the stages of AS by regulating downstream pathways. Ultimately, circRNAs play very important roles in AS by regulating inflammation, apoptosis, and some other mechanisms. The study of circular RNAs can provide new ideas for the prediction, prevention, and treatment of AS.

Keywords: atherosclerosis; cell apoptosis; cell migration; cell proliferation; circular RNA (circRNA); inflammation.

Figure 1

Molecular mechanism of circ_ANRIL controlling PeBoW complex fuction. (A) PeBoW complex assembles with the pre-ribosome and binds the precursor rRNA (pre-rRNA), thereby facilitating the processing of 47S pre-rRNA into mature 28S and 5.8S rRNAs by nucleic acid exonucleases. (B) Lesca et al. found a strong interaction between circRNA and PES1 by RNA immunoprecipitation (RIP). (C) Circ_ANRIL binding to the complex of PES1 inhibited the formation of PeBoW complex, thus suppressing the formation of 28S and 5.8S rRNAs. Abbreviation: ANRIL: circ_ANRIL; PES1: pescadillo homologue1; BOP1: block of proliferation 1; and WDR12: WD-repeat protein 12.

Figure 2

Major pathways of action of circ_CHFR in AS. (a) Downregulation of circ_CHFR inhibits the expression of FOXO1 as well as Cyclin D1 through upregulating activity of miR-370 ultimately causing a reduction in cell proliferation and migration. (b) Downregulation of circ_CHFR inhibits Wnt3 expression through upregulating activity of miR-214-3p ultimately causing a decrease in cell proliferation and migration. (c) Downregulation of circ_CHFR by upregulating activity of miR-15a-5p binds to EGFR and ultimately causes a decrease in the G0/G1 ratio in the cell cycle. (d) Unlike previous studies, downregulation of circ_CHFR promotes cell proliferation and, in addition, causes a decrease in apoptosis.