TY - JOUR
T1 - Circular RNA circSmoc1-2 regulates vascular calcification by acting as a miR-874-3p sponge in vascular smooth muscle cells
AU - Ryu, Juhee
AU - Choe, Nakwon
AU - Kwon, Duk Hwa
AU - Shin, Sera
AU - Lim, Yeong Hwan
AU - Yoon, Gwangho
AU - Kim, Ji Hye
AU - Kim, Hyung Seok
AU - Lee, In Kyu
AU - Ahn, Youngkeun
AU - Park, Woo Jin
AU - Kook, Hyun
AU - Kim, Young Kook
N1 - Publisher Copyright:
© 2021 The Author(s)
PY - 2022/3/8
Y1 - 2022/3/8
N2 - 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 circSmoc1-2 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 circSmoc1-2 may be a novel therapeutic target in the treatment of VC.
AB - 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 circSmoc1-2 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 circSmoc1-2 may be a novel therapeutic target in the treatment of VC.
KW - Adam19
KW - Circular RNA
KW - circSmoc1-2
KW - miRNA-874-3p
KW - vascular calcification
KW - vascular smooth muscle cells
UR - http://www.scopus.com/inward/record.url?scp=85122620374&partnerID=8YFLogxK
U2 - 10.1016/j.omtn.2021.12.031
DO - 10.1016/j.omtn.2021.12.031
M3 - Article
AN - SCOPUS:85122620374
SN - 2162-2531
VL - 27
SP - 645
EP - 655
JO - Molecular Therapy Nucleic Acids
JF - Molecular Therapy Nucleic Acids
ER -
