Circular RNA circSmoc1-2 regulates vascular calcification by acting as a miR-874-3p sponge in vascular smooth muscle cells

Abstract

Vascular calcification (VC), or calcium deposition inside the blood vessels, is common in patients with atherosclerosis, cardiovascular disease, and chronic kidney disease. Although several treatments are available to reduce calcification, the incidence of VC continues to rise. Recently, there have been several reports describing the regulation of circular RNAs (circRNAs) in various diseases. However, the role of circRNAs in VC has not yet been fully explored. Here, we investigated the function of circSmoc1-2, one of the circRNAs generated from the Smoc1 gene, which is downregulated in response to VC. CircSmoc1-2 is localized primarily to the cytoplasm and is resistant to exonuclease digestion. Inhibition of circSmoc1-2 worsens VC, while overexpression of circSmoc1-2 reduces VC, suggesting that circSmoc1-2 can prevent calcification. We went on to investigate the mechanism of circSmoc1-2 as a microRNA sponge and noted that miR-874-3p, the predicted target of circSmoc1-2, promotes VC, while overexpression of circS-moc1-2 reduces VC by suppressing miR-874-3p. Additionally, we identified the potential mRNA target of miR-874-3p as Adam19. In conclusion, we revealed that the circSmoc1-2/ miR-874-3p/Adam19 axis regulates VC, suggesting that circS-moc1-2 may be a novel therapeutic target in the treatment of VC.

Identification of potential biomarkers of vascular calcification using bioinformatics analysis and validation in vivo

“…miR-134-5p exacerbates vascular calcification by regulating the expression of histone deacetylase 5 in high phosphate conditions ( Choe et al, 2020b ). CircSmoc1-2 attenuates vascular calcification by regulating the miR-874-3p/Adam19 axis ( Ryu et al, 2022 ). miR-26-5p affects the pathological process of VC in patients with chronic kidney disease by regulating PTEN expression ( Chang et al, 2020 ).…”

Upregulation of hsa_circ_0000977 participates in esophageal squamous cancer progression by sponging miR‐874‐3p

“…To explore how the hsa_circ_0000977 sponge affects the downstream pathway after miR‐874‐3p, 24 we predicted the target miR‐874‐3p using Targetscan, 25 TarBase, 26 and ENCORI 27 . After interactive analysis of these groups of predicted target genes, three highly reliable target genes were identified (TP53INP2, OSTM1, and KMT2D).…”

Profiling and Cellular Analyses of Obesity-Related circRNAs in Neurons and Glia under Obesity-like In Vitro Conditions

“…Among various factors, neuronal PAS domain protein 4 (NPAS4), SRY-box transcription factor 8 (SOX8), and retinoid X receptor gamma (RXRG) were shown to be highly likely to interact with circSnx12 and circUsp3, which have low protein-coding potential ( Figure 6 G,I). NPAS4 is known to play an important role in contextual memory formation in the CA3 region of the hippocampus as a transcriptional factor [ 42 ]. SOX8 has been reported to enhance the astrogenesis of neural stem and precursor cells by targeting Nfia [ 43 ].…”