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

Juhee Ryu; Nakwon Choe; Duk-Hwa Kwon; Sera Shin; Yeong-Hwan Lim; Gwangho Yoon; Ji Hye Kim; Hyung Seok Kim; In-Kyu Lee; Youngkeun Ahn; Woo Jin Park; Hyun Kook; Young-Kook Kim

Molecular Therapy: Nucleic Acids (Mar 2022)

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

Juhee Ryu,
Nakwon Choe,
Duk-Hwa Kwon,
Sera Shin,
Yeong-Hwan Lim,
Gwangho Yoon,
Ji Hye Kim,
Hyung Seok Kim,
In-Kyu Lee,
Youngkeun Ahn,
Woo Jin Park,
Hyun Kook,
Young-Kook Kim

Affiliations

Juhee Ryu: Chonnam University Research Institute of Medical Sciences, Jeollanam-do, Republic of Korea; The BK21 FOUR Center for Glocal Future Biomedical Scientists at Chonnam National University Medical School, Jeollanam-do, Republic of Korea; Basic Research Laboratory for Vascular Remodeling, Chonnam National University Medical School, Jeollanam-do, Republic of Korea; College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu, Republic of Korea; Department of Pharmacology, Chonnam National University Medical School, Jeollanam-do, Republic of Korea; Department of Biochemistry, Chonnam National University Medical School, Jeollanam-do, Republic of Korea
Nakwon Choe: Basic Research Laboratory for Vascular Remodeling, Chonnam National University Medical School, Jeollanam-do, Republic of Korea; Department of Pharmacology, Chonnam National University Medical School, Jeollanam-do, Republic of Korea
Duk-Hwa Kwon: The BK21 FOUR Center for Glocal Future Biomedical Scientists at Chonnam National University Medical School, Jeollanam-do, Republic of Korea; Basic Research Laboratory for Vascular Remodeling, Chonnam National University Medical School, Jeollanam-do, Republic of Korea; Department of Pharmacology, Chonnam National University Medical School, Jeollanam-do, Republic of Korea
Sera Shin: Basic Research Laboratory for Vascular Remodeling, Chonnam National University Medical School, Jeollanam-do, Republic of Korea; Department of Pharmacology, Chonnam National University Medical School, Jeollanam-do, Republic of Korea
Yeong-Hwan Lim: Basic Research Laboratory for Vascular Remodeling, Chonnam National University Medical School, Jeollanam-do, Republic of Korea; Department of Biochemistry, Chonnam National University Medical School, Jeollanam-do, Republic of Korea
Gwangho Yoon: The BK21 FOUR Center for Glocal Future Biomedical Scientists at Chonnam National University Medical School, Jeollanam-do, Republic of Korea; Department of Biochemistry, Chonnam National University Medical School, Jeollanam-do, Republic of Korea
Ji Hye Kim: Chonnam National University Hwasun Hospital Biomedical Research Institute, Jeollanam-do, Republic of Korea
Hyung Seok Kim: Department of Forensic Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea
In-Kyu Lee: Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Republic of Korea
Youngkeun Ahn: Basic Research Laboratory for Vascular Remodeling, Chonnam National University Medical School, Jeollanam-do, Republic of Korea; Department of Cardiology, Cardiovascular Center, Chonnam National University Hospital, Gwangju, Republic of Korea
Woo Jin Park: Basic Research Laboratory for Vascular Remodeling, Chonnam National University Medical School, Jeollanam-do, Republic of Korea; College of Life Sciences, Gwangju Institute of Science and Technology (GIST), Gwangju, Republic of Korea
Hyun Kook: Basic Research Laboratory for Vascular Remodeling, Chonnam National University Medical School, Jeollanam-do, Republic of Korea; Department of Pharmacology, Chonnam National University Medical School, Jeollanam-do, Republic of Korea; Corresponding author: Hyun Kook, Department of Pharmacology, Chonnam National University Medical School, Jeollanam-do, Republic of Korea.
Young-Kook Kim: Basic Research Laboratory for Vascular Remodeling, Chonnam National University Medical School, Jeollanam-do, Republic of Korea; Department of Biochemistry, Chonnam National University Medical School, Jeollanam-do, Republic of Korea; Corresponding author: Young-Kook Kim, Department of Biochemistry, Chonnam National University Medical School, Jeollanam-do, Republic of Korea.

Journal volume & issue: Vol. 27
pp. 645 – 655

Abstract

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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.

Published in Molecular Therapy: Nucleic Acids

ISSN: 2162-2531 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: https://www.cell.com/molecular-therapy-family/nucleic-acids/latest-content

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