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

doi:10.1016/j.omtn.2021.12.031

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

Mol Ther Nucleic Acids. 2021 Dec 22:27:645-655. doi: 10.1016/j.omtn.2021.12.031. eCollection 2022 Mar 8.

Authors

Juhee Ryu^{1

2

3

4

5

6}, Nakwon Choe^{3

5}, Duk-Hwa Kwon^{2

3

5}, Sera Shin^{3

5}, Yeong-Hwan Lim^{3

6}, Gwangho Yoon^{2

6}, Ji Hye Kim⁷, Hyung Seok Kim⁸, In-Kyu Lee⁹, Youngkeun Ahn^{3

10}, Woo Jin Park^{3

11}, Hyun Kook^{3

5}, Young-Kook Kim^{3

6}

Affiliations

¹ Chonnam University Research Institute of Medical Sciences, Jeollanam-do, Republic of Korea.
² The BK21 FOUR Center for Glocal Future Biomedical Scientists at Chonnam National University Medical School, Jeollanam-do, Republic of Korea.
³ Basic Research Laboratory for Vascular Remodeling, Chonnam National University Medical School, Jeollanam-do, Republic of Korea.
⁴ College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu, Republic of Korea.
⁵ Department of Pharmacology, Chonnam National University Medical School, Jeollanam-do, Republic of Korea.
⁶ Department of Biochemistry, Chonnam National University Medical School, Jeollanam-do, Republic of Korea.
⁷ Chonnam National University Hwasun Hospital Biomedical Research Institute, Jeollanam-do, Republic of Korea.
⁸ Department of Forensic Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea.
⁹ Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Republic of Korea.
¹⁰ Department of Cardiology, Cardiovascular Center, Chonnam National University Hospital, Gwangju, Republic of Korea.
¹¹ College of Life Sciences, Gwangju Institute of Science and Technology (GIST), Gwangju, Republic of Korea.

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 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.

Keywords: Adam19; Circular RNA; circSmoc1-2; miRNA-874-3p; vascular calcification; vascular smooth muscle cells.