The Role of Circular RNAs in Immune-Related Diseases

Abstract

Circular RNAs (circRNAs) are a novel class of RNAs with a covalently closed loop structure without a 3 ′ polyadenylation [poly-(A)] tail or a 5 ′ cap. They used to be considered as the occasional and useless products of RNA splicing errors because they could not be detected by traditional RNA sequencing technology. Benefiting from the development of specific biochemical and computational approaches, researchers showed that circRNAs are universally expressed and functional. Further studies have revealed their important functions regarding regulating gene expression at the transcriptional and post-transcriptional levels. These functions include acting as microRNA (miRNA) sponges, binding to RNA-binding proteins (RBPs), acting as transcriptional regulatory factors, and serving as translation templates. The advances in circRNA research has opened researchers' eyes to a new area of research on the roles of circRNAs in the pathogenesis of various diseases, especially at the immune level because of the close relationship between circRNAs and the immune response. Emerging research indicates that circRNAs could act as potential biomarkers related to diagnosis, therapeutic effects, and prognosis, and they may be effective therapeutic targets in immunological disorders, including certain diseases that are currently difficult to treat.

Epigenetic modification mechanisms involved in keloid: current status and prospect

“…CircRNAs, consisting of covalently closed continuous loops, are a newly identified type of ncRNAs with the ability to encode proteins, regulate gene transcription, and act as a special “sponge” for miRNAs and harbor abundant miRNA binding sites [ 44 ]. Unlike the above two linear miRNAs and lncRNAs, due to the 3′ and 5′ ends commonly presented are firmly concatenated, circRNAs exist in multiple species with high abundance, high sequence conservation, and specific expression [ 45 , 46 ]. Aberrant circRNAs expression plays a crucial regulatory role during the occurrence and development of fibrosis diseases, including hepatic fibrosis, cardiac fibrosis, and keloid.…”

Emerging roles of circular RNAs in systemic lupus erythematosus

“…Although studies on the biological functions and mechanisms underlying the effects of circRNAs in autoimmune diseases are finite, a considerable number of studies have revealed their effects on molecular biological processes and immune regulation of various immune cells. 7 , 62 , 63 , 64 For instance, circ-ANRIL induces nucleolar stress and p53 activation, resulting in the apoptosis elevation and proliferation suppression in macrophages. 65 circRNA-002178 can be delivered by exosomes into CD8 T cells to induce PD1 expression, leading to T cell exhaustion.…”

The expanding role of CDR1‐AS in the regulation and development of cancer and human diseases

“…Present studies have revealed that miR‐7 can regulate α‐synuclein by directly binding to SNCA gene 3′‐untranslated region; and a decreased level of miR‐7 is seen in substantia nigra of PD patients. As high expression of CDR1‐AS is seen in human and mouse brain and due to its role in miR‐7 sponging, it is believed that this circle RNA may be a good target as a therapeutic target for PD (Junn et al, 2009; Xie, Zhang, Zhang, Li, & Zhou, 2020).…”