circSPG21 protects against intervertebral disc disease by targeting miR-1197/ATP1B3

Yizhen Huang; Zhenlei Zhang; Jianle Wang; Shuying Shen; Teng Yao; Yining Xu; Zizheng Chen; Bin Fang; Jianjun Ma

doi:10.1038/s12276-021-00674-z

circSPG21 protects against intervertebral disc disease by targeting miR-1197/ATP1B3

Exp Mol Med. 2021 Oct;53(10):1547-1558. doi: 10.1038/s12276-021-00674-z. Epub 2021 Oct 6.

Authors

Yizhen Huang^#^{1

2}, Zhenlei Zhang^#^{1

2}, Jianle Wang^#^{1

2}, Shuying Shen^{1

2}, Teng Yao^{1

2}, Yining Xu³, Zizheng Chen^{1

2}, Bin Fang⁴, Jianjun Ma^{5

6}

Affiliations

¹ Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Zhejiang, China.
² Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang Province, Zhejiang, China.
³ Shaoxing University School of Medicine, Shaoxing, China.
⁴ Department of Spine Surgery, Shaoxing Central Hospital, China Medical University, Shaoxing, China. fangbin008@outlook.com.
⁵ Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Zhejiang, China. sealteam@zju.edu.cn.
⁶ Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang Province, Zhejiang, China. sealteam@zju.edu.cn.

^# Contributed equally.

Abstract

The abnormal expression of circular RNAs (circRNAs) is associated with numerous human diseases. This study investigated the mechanism by which circRNA acts as competitive endogenous RNA in the regulation of degenerative intervertebral disc disease (IVDD). Decreased expression of circSPG21 was detected in degenerated nucleus pulposus cells (NPCs), the function of circSPG21 in NPCs was explored and verified, and the downstream target of circSPG21 was investigated. The interaction between circSPG21 and miR-1197 and its target gene (ATP1B3) was studied by online database prediction and molecular biological verification. Finally, the circSPG21/miR-1197/ATP1B3 axis was verified in the mouse tail-looping model. The expression of circSPG21 in the nucleus pulposus in IVDD was directly related to an imbalance of anabolic and catabolic factors, which affected cell senescence. circSPG21 was found to play a role in human NPCs by acting as a sponge of miR-1197 and thereby affecting ATP1B3. The regulation of circSPG21 provides a potentially effective therapeutic strategy for IVDD.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Apoptosis / genetics
Intervertebral Disc Degeneration* / genetics
Intervertebral Disc Degeneration* / metabolism
Intervertebral Disc Displacement
Mice
MicroRNAs* / genetics
MicroRNAs* / metabolism
Nucleus Pulposus* / metabolism

Substances

MicroRNAs

Supplementary concepts

Intervertebral disc disease