Circular RNA VMA21 protects against intervertebral disc degeneration through targeting miR-200c and X linked inhibitor-of-apoptosis protein
Open accessAbstract
OBJECTIVES: Circular RNAs (circRNAs) have been proven to function as competing endogenous RNAs to interact with microRNAs (miRNAs) and influence the expression of miRNA target mRNAs. In this study, we investigated whether circRNAs could act as competing endogenous RNAs to regulate the pathological process of intervertebral disc degeneration (IVDD). METHODS: The role and mechanism of a circRNA, circVMA21, in IVDD were explored in nucleus pulposus (NP) cells and degenerative NP tissues from patients and rat models. The interaction between circVMA21 and miR-200c as well as the target mRNA, X linked inhibitor-of-apoptosis protein (XIAP), was examined. RESULTS: The decreased expression of XIAP in the inflammatory cytokines-treated NP cells and the degenerative NP tissues was directly associated with excessive apoptosis and imbalance between anabolic and catabolic factors of extracellular matrix. miR-200c regulated NP cell viability and functions through inhibiting XIAP. circVMA21 acted as a sponge of miR-200c and functioned in NP cells through targeting miR-200c and XIAP. Intradiscal injection of circVMA21 alleviated IVDD in the rat model. CONCLUSIONS: CircVMA21 could alleviate inflammatory cytokines-induced NP cell apoptosis and imbalance between anabolism and catabolism of extracellular matrix through miR-200c-XIAP pathway. It provides a potentially effective therapeutic strategy for IVDD.
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miRNAs play a key role in post-transcriptional regulation and circRNAs function as miRNA sequesters to modulate the pathogenesis and progression of various diseases.
“It is well known that miRNAs play a key role in post-transcriptional regulation and circRNAs function as miRNA sequesters to modulate the pathogenesis and progression of various diseases.32,52”
From Microglia secrete miR-146a-5p-containing exosomes to regulate neurogenesis in depression (2022) · cites this paper as [52]
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Self-citation
- Authors
- Cheng, X., Zhang, L., Zhang, K., Zhang, G., Hu, Y., Sun, X., Zhao, C., Li, H., Li, Y. M., & Zhao, J.
- Affiliations
- Shanghai Jiao Tong University (CN)
- Yangzhou University (CN)
- Chinese People's Liberation Army (CN)
- Shanghai Municipal Center For Disease Control Prevention (CN)
- University of Rochester Medicine (US)
- Corresponding author
- Zhao, Jie
- Venue
- Annals of the Rheumatic Diseases
- Publisher
- Elsevier BV
- Published
- 2018-05
- Volume
- 77
- Issue
- 5
- Pages
- 770-779
- ISSN
- 0003-4967 (ISSN-L)
- PMC
- PMC5909753
- OpenAlex
- W2783392754
- Cited by
- 280
- References
- 43
- Citations by year
- 2026: 7 · 2025: 18 · 2024: 17 · 2023: 35 · 2022: 57 · 2021: 48 · 2020: 56 · 2019: 34 · 2018: 7
- FWCI
- 12.89
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Annals of the Rheumatic Diseases (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- The National Natural Science Foundation of China
- The Natural Science Foundation of Shanghai
- The Fundamental Research Program Funding of Ninth People’s Hospital affiliated to Shanghai Jiao Tong University School of Medicine
- The Industry-Academy-Research Cooperation Project of Shanghai Science and Technology Committee
- The Department Integration Foundation of Shanghai Ninth People’s Hospital
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Circular RNAs in diseases
- Health Sciences › Medicine › Pathology and Forensic Medicine › Spine and Intervertebral Disc Pathology
- Health Sciences › Medicine › Rheumatology › Osteoarthritis Treatment and Mechanisms
- Keywords
- intervertebral disc degeneration, miR-200c, XIAP, competing endogenous RNA, nucleus pulposus cells, apoptosis, inflammatory cytokines, intradiscal injection, therapeutic target
- MeSH terms
- Nucleus Pulposus, RNA, Circular, Animals, Cell Survival, Extracellular Matrix, Humans, RNA, Signal Transduction, Apoptosis, Vacuolar Proton-Translocating ATPases, MicroRNAs, Rats, X-Linked Inhibitor of Apoptosis Protein, Intervertebral Disc Degeneration
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