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Review
. 2021 Nov 10:26:1291-1302.
doi: 10.1016/j.omtn.2021.11.007. eCollection 2021 Dec 3.

Role of circRNA-miRNA-mRNA interaction network in diabetes and its associated complications

Shukla Sakshi  1 , Ravichandran Jayasuriya  1 , Kumar Ganesan  2   3 , Baojun Xu  3 , Kunka Mohanram Ramkumar  1
Affiliations
Review

Role of circRNA-miRNA-mRNA interaction network in diabetes and its associated complications

Shukla Sakshi et al. Mol Ther Nucleic Acids. .

Abstract

The majority of the non-protein-coding RNAs are being identified with diversified functions that participate in cellular homeostasis. The circular RNAs (circRNAs) are emerging as noncoding transcripts with a key role in the initiation and development of many physiological and pathological conditions. The advancements in high-throughput RNA sequencing and bioinformatics tools help us to identify several circRNA regulatory pathways, one of which is microRNA (miRNA)-mediated regulation. Besides the direct influence over mRNA transcription, the circRNA can also control the target's expression via sponging miRNAs or the RNA-binding proteins. Studies have demonstrated the dysregulation of the circRNA-miRNA-mRNA interaction network in the pathogenesis of many diseases, including diabetes. This intricate mechanism is associated with the pathogenesis of diabetes and its complications. This review will focus on the circRNA-miRNA-mRNA interaction network that influences the gene expression in the progression of diabetes and its associated complications.

Keywords: circRNA-miRNA-mRNA; diabetes; diabetic complications.

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Conflict of interest statement

The authors declare no competing interests.

Figures

None
Graphical abstract
Figure 1
Figure 1
Biogenesis of circRNA (A) In lariat-driven circularization, the formation of exonic circRNA is through exon skipping guided by a splice acceptor/donor. (B) In intron pairing-driven circularization, the formation of intronic or exon-intronic circRNA is by the hybridization of flanking introns with close proximity and is independent of exon skipping and brings the splice site.
Figure 2
Figure 2
Functions of circRNA The intronic and exon-intronic circRNAs act on the promotor region to recruit Pol II, thereby promoting transcription of target genes. The exonic circRNA that is exported to the cytoplasm functions as an miRNA sponge and sequesters the endogenous miRNA that inhibits target mRNA (A), or binds with RNA-binding proteins and act as a protein sponge and mediates their action (B). m6A and IRES modification can promote circRNA to translate to a protein (C). RBP, RNA-binding protein.
Figure 3
Figure 3
circRNA-miRNA-mRNA interaction in diabetes and its complications The circRNAs negatively regulate the miRNA, which inhibits the expression of mRNA.
Figure 4
Figure 4
Construction of circRNA-miRNA-mRNA interaction network The step-wise construction of circRNA-miRNA-mRNA interaction network using bioinformatics tools. ∗Differentially expressed circRNAs (DECs), differentially expressed miRNAs (DEMs), and differentially expressed genes (DEGs).
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