Exploring the Multifaceted Biologically Relevant Roles of circRNAs: From Regulation, Translation to Biomarkers

Abstract

CircRNAs are a category of regulatory RNAs that have garnered significant attention in the field of regulatory RNA research due to their structural stability and tissue-specific expression. Their circular configuration, formed via back-splicing, results in a covalently closed structure that exhibits greater resistance to exonucleases compared to linear RNAs. The distinctive regulation of circRNAs is closely associated with several physiological processes, as well as the advancement of pathophysiological processes in several human diseases. Despite a good understanding of the biogenesis of circular RNA, details of their biological roles are still being explored. With the steady rise in the number of investigations being carried out regarding the involvement of circRNAs in various regulatory pathways, understanding the biological and clinical relevance of circRNA-mediated regulation has become challenging. Given the vast landscape of circRNA research in the development of the heart and vasculature, we evaluated cardiovascular system research as a model to critically review the state-of-the-art understanding of the biologically relevant functions of circRNAs. We conclude the review with a discussion of the limitations of current functional studies and provide potential solutions by which these limitations can be addressed to identify and validate the meaningful and impactful functions of circRNAs in different physiological processes and diseases.

Development of an efficient, effective, and economical technology for proteome analysis

“…Circular RNAs (circRNAs) are a recently appreciated class of regulatory RNAs, which regulate gene expression primarily by either sponging microRNAs (miRNAs) or interacting with RBPs. 33 The interactions of circRNAs with RBPs are less well studied as compared to their binding to miRNAs, mainly due to the lack of robust and reliable technologies to identify their interactions. Affinity purification (AP) followed by MS-based quantitative proteomic approaches has been utilized widely as an unbiased way to identify protein-RNA interactions.…”

The therapeutic potential of circular RNA in triple-negative breast cancer

“…The vast majority of circRNAs have corresponding linear parental genes in organisms, which makes it difficult to be distinguished easily. Currently, the main approach is first to enrich circRNAs based on their unique stable structure by digesting total RNA with RNase R, and then to identify specific circRNAs through the detection of specific junction sequences by RNA high-throughput sequencing [ 29 ] . Although these methods can identify many BSJ sequences, their detection sensitivity is low once the BSJ sequence is very short.…”

Communication molecules (ncRNAs) mediate tumor-associated macrophage polarization and tumor progression

“…CircRNAs' participation spans diverse cellular processes, encompassing domains such as cerebral function, immune responsiveness, and oncogenic pathways (Mehta et al, 2020;Li B. et al, 2021). The cyclic nature of circRNAs imparts enhanced stability when contrasted with linear RNA counterparts (Hoque et al, 2023).…”