Hsa_circ_0134111 promotes intervertebral disc degeneration via sponging miR-578

Abstract

Intervertebral disc degeneration (IDD) is a chronic degenerative and age-dependent process characterized by aberrant apoptosis, proliferation, synthesis, and catabolism of the extracellular matrix of the nucleus pulposus (NP) cells. Recently, studies showed that circular RNAs play important roles in the development of many diseases. However, the role of circRNAs in IDD development remains unknown. We showed that circ_0134111 level was overexpressed in IDD tissue samples as compar-ed to control tissues. The upregulation of circ_0134111 was more drastic in the moderate and severe IDD cases than in those with mild IDD. In addition, we showed that interleukin-1β and tumor necrosis factor-α exposure significantly enhanced circ_0134111 expression in NP cells. Furthermore, ectopic expression of circ_0134111 induced proliferation, pro-inflammatory cytokine secretion, and ECM degradation in the NP cells. We also showed that circ_0134111 directly interacted with microRNA (miR)-578 in NP cells where elevated expression of circ_0134111 enhanced the ADAMTS-5 and MMP-9 expression. Moreover, miR-578 expression was significantly decreased in IDD patients and the miR-578 expression was negatively correlated with circ_0134111 expression in the IDD samples. Interleukin-1β and tumor necrosis factor-α exposure significantly decreased miR-578 levels in NP cells, in which ectopic miR-578 expression inhibited cell growth, pro-inflammatory cytokine expression, and ECM degradation. Finally, we showed that circ_0134111 overexpression induced the IDD-related phenotypic changes through inhibiting miR-578. These data suggested that circ_0134111 could promote the progression of IDD through enhancing aberrant NP cell growth, inflammation, and ECM degradation partly via regulating miR-578.

Exosomal circFAM63Bsuppresses bone regeneration of postmenopausal osteoporosis via regulating miR‐578/HMGA2 axis

“…However, the roles of miR‐578 in osteogenesis remain unclear. Yan et al 36 found that miR‐578 expression was significantly decreased in IDD patients and played positive roles in protecting ECM degradation. We determined that miR‐578 is downregulated in PMOP and negatively correlated with the expression level of circFAM63B.…”

Identification and experimental validation of key extracellular proteins as potential targets in intervertebral disc degeneration

“… 72 Interleukin-1β and TNF-α exposure greatly reduced miR-578 levels in nucleus pulposus, where ectopic miR-578 expression inhibited cell growth, proinflammatory cytokine expression, and ECM degradation. 73 Moreover, the DSigDB database was used to predict several drugs, which are related to the hub EP-DEGs. Among all the candidate drugs, this study shows the top ten most notable drugs, which includes electrocorundum, phenytoin, cytarabine, testosterone enanthate, paclitaxel alpha-Neu5Ac, acetaldehyde, and sorafenib.…”

Regulatory roles of noncoding RNAs in intervertebral disc degeneration as potential therapeutic targets (Review)

“…Based on animal models, it is possible to slow down or stop the progression of IDD by boosting, lowering or eliminating the expression of one or more particular miRNAs, lncRNAs and circRNAs in vivo ( 21 , 44 ). To date, most studies have primarily focused on disease samples, cells and small animals, which are dissimilar from the biomechanics of humans ( 106 , 107 ). Therefore, there is an urgent need for an improved animal model of the human spine.…”

“…In addition, they reported that circ_0134111 causes osteoarthritis progression via targeting miR-224-5p and regulating C-C motif chemokine ligand 1. Recently, Yan et al ( 106 ) found that circ_0134111 expression is significantly upregulated in IDD tissue and the elevation of circ_0134111 is greater in severe IDD cases. In addition, they discovered that IL-1β and TNF-α significantly increase circ_0134111 expression in NP cells.…”