Expression profiling of circular RNAs and their potential role in early‑stage diabetic cardiomyopathy

Abstract

diabetic cardiomyopathy (dcM) is a severe cardiovascular complication of diabetes mellitus (dM). detecting dcM during the early stages of the disease remains a challenge, as the molecular mechanisms underlying early-stage dcM are not clearly understood. circular rna (circrna), a type of non-coding RNA, has been confirmed to be associated with numerous diseases. However, it is still unclear how circrnas are involved in early-stage dcM. in the present study, heart tissues harvested from BKS-db/db knockout mice were identified through high-throughput rna sequencing technology. A total of 58 significantly differentially expressed circRNAs were identified in the db/db sample. Among these, six upregulated circRNAs and seven downregulated circRNAs were detected by reverse transcription-quantitative Pcr and analyzed using Gene ontology and Kyoto encyclopedia of Genes and Genomes. Furthermore, based on the predicted binding site with microRNAs (miRNAs) involved in DCM, five circrnas (mmu_circ_0000652, mmu_circ_0000547, mmu_ circ_0001058, mmu_circ_0000680 and novel_circ_0004285) were shown to serve as competing endogenous (ce)rnas. The corresponding mirnas and mrnas of the cernas were also verified, and two promising circRNA-miRNA-mRNA regulatory networks were determined. Finally, internal ribosome entry site prediction combined with open reading frame prediction indicated that it was highly possible that mmu_circ_0001160 encoded a protein. in the present study, a comprehensive analysis of the circRNA expression profile during the early phase of dcM was performed, and two promising circrna-mirna-mrna regulatory networks were identified. These results lay the foundation for unravelling the underlying pathogenesis of dcM, and highlight potential biomarkers and therapeutic targets for the treatment of dcM at an early stage.

Circular RNA mediated gene regulation in chronic diabetic complications

“…Other circular RNAs, altered in diabetic retinopathy include circular DNMT3B and circRNA_0084043, each working through various pathways 24 , 25 . In the heart, 58 significantly differentially expressed circRNAs were identified in db/db mice, a model of type 2 diabetes 26 . Also identified are alterations of circRNA_010567 and circRNA_000203 working through various pathways to regulate specific transcript altering fibrosis related genes 27 , 28 .…”

Insights into circular RNAs: Biogenesis, function and their regulatory roles in cardiovascular disease

“…However, the specific pathway has yet to be further verified. 147 Furthermore, Yang et al 148 Although research on circRNAs in CVDs is just emerging when compared with other research fields, such as cancer and neurological disorders, multiple studies have confirmed that circRNAs with stable, highly conserved and longer half-lives have bright prospects as candidate biomarkers and treatment targets for CVDs.…”

“…Subsequent functional analysis indicated that these differentially expressed circRNAs and their target mRNAs were mainly involved in the regulatory pathways of glycolipid metabolism. However, the specific pathway has yet to be further verified 147 . Furthermore, Yang et al 148 found that hsa_circ_0076631, a novel circRNA named caspase‐1‐associated circRNA (CACR), was significantly elevated in both DCM cardiomyocytes and the serum of diabetic patients.…”

Circular RNAs: New Players in Cardiomyopathy

“…Dong et al [ 107 ] carried out high-throughput RNA sequencing on the myocardium of a mouse model in order to identify circRNA expression. They determined that 58 circRNAs were markedly differentially expressed.…”