CircRNA-CIDN mitigated compression loading-induced damage in human nucleus pulposus cells via miR-34a-5p/SIRT1 axis

• Published in: EBioMedicine Vol. 53; p. 102679
• Main Authors: Xiang, Qian, Kang, Liang, Wang, Juntan, Liao, Zhiwei, Song, Yu, Zhao, Kangcheng, Wang, Kun, Yang, Cao, Zhang, Yukun
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier 01.03.2020
• Subjects: Animals; Apoptosis; Cells, Cultured; Extracellular Matrix - metabolism; Extracellular Matrix - pathology; HEK293 Cells; Humans; Intervertebral Disc Degeneration - genetics; Intervertebral Disc Degeneration - metabolism; Male; MicroRNAs - genetics; MicroRNAs - metabolism; Nucleus Pulposus - metabolism; Nucleus Pulposus - pathology; Rats; Rats, Sprague-Dawley; Research paper; RNA, Circular - genetics; RNA, Circular - metabolism; Sirtuin 1 - genetics; Sirtuin 1 - metabolism; Weight-Bearing; Intervertebral disc degeneration; Compression; miR-34a-5p/SIRT1 axis; Circular RNAs; Nucleus pulposus cell
• ISSN: 2352-3964; 2352-3964
• DOI: 10.1016/j.ebiom.2020.102679

Intervertebral disc degeneration (IDD) is a major contributor to lower back pain, however, the molecular and pathogenetic mechanisms underlying IDD are poorly understood. As a high-risk factor for IDD, compression stress was reported to induce apoptosis of nucleus pulposus (NP) cells and extracellular matrix (ECM) degradation during IDD progression. Circular RNA (circRNA) is a class of endogenous non-coding RNA (ncRNA) and has been reported to function in several diseases. However, whether and how circRNA regulates compression-induced damage of NP cells remains vague. Here, we aimed to investigate the key role of circRNA in compression loading-induced IDD. We analysed the circRNA expression of three samples from compression-treated NP cells and three control samples using circRNA microarray assays and further investigated the circRNA involved in compression-induced damage of NP cells (circRNA-CIDN). We investigated the effects of circRNA-CIDN on compression-induced cell apoptosis and NP ECM degradation in vitro and ex vivo. We observed that circRNA-CIDN bound to miRNAs as a miRNA sponge based on luciferase and RNA immunoprecipitation (RIP) assays. CircRNA-CIDN was significantly downregulated in compression-treated human NP cells, as validated by circRNA microarray and qRT-PCR analysis, and overexpressing circRNA-CIDN inhibited compression-induced apoptosis and NP ECM degradation. Further studies demonstrated that circRNA-CIDN served as a sponge for miR-34a-5p, an important miRNA that enhanced compression-induced damage of NP cells via repressing the silent mating type information regulation 2 homolog 1 (SIRT1). CircRNA-CIDN was also verified to contain IDD development in an ex vivo IDD model. Our results revealed that circRNA-CIDN binding to miR-34a-5p played an important role in mitigating compression loading-induced nucleus pulposus cell damage via targeting SIRT1, providing a potential therapeutic strategy for IDD treatment. National Natural Science Foundation of China (81772391, 81974348), Fundamental Research Funds for the Central Universities (2017KFYXJJ248).