CircSEMA4B targets miR-431 modulating IL-1beta-induced degradative changes in nucleus pulposus cells in intervertebral disc degeneration via Wnt pathway
Title | CircSEMA4B targets miR-431 modulating IL-1beta-induced degradative changes in nucleus pulposus cells in intervertebral disc degeneration via Wnt pathway |
Publication Type | Journal Article |
Year of Publication | 2018 |
Authors | Wang, X, Wang, B, Zou, M, Li, J, Lu, G, Zhang, Q, Liu, F, Lu, C |
Journal | Biochim Biophys Acta Mol Basis Dis |
Volume | 1864 |
Pagination | 3754-3768 |
Date Published | Nov |
ISBN Number | 0925-4439 |
Accession Number | 30251693 |
Keywords | *Circular RNA SEMA4B (circSEMA4B), *Intervertebral disc degeneration (idd), *miR-431, *Nucleus pulposus cells (NPCs), *Wnt signaling |
Abstract | Intervertebral disc (IVD) degeneration (IDD), characterized by elevated levels of proinflammatory mediators, increased Aggrecan and collagen degradation, and increased degradation of extracellular matrix (ECM), has been widely regarded as a significant contributor to low back pain. Genetics are significant factors contribute to IDD. Based on previous data, circular RNA SEMA4B (circSEMA4B) is down-regulated in IDD specimens; herein, we demonstrated circSEMA4B overexpression could attenuate the effect of IL-1beta on nucleus pulposus cell (NPC) proliferation, senescence, and ECM and Aggrecan degradation in IDD via Wnt signaling. Moreover, miR-431, a direct target of circSEMA4B, could bind to the 3'UTR of SFRP1 or GSK-3beta, two inhibitory regulators of Wnt signaling, to inhibit their expression thus playing a role similar to the activator of Wnt signaling in NPCs. The effect of circSEMA4B knockdown on NPCs was partially reversed by miR-431 inhibition; circSEMA4B serves as a miR-431 sponge to compete with SFRP1 or GSK-3beta for miR-431 binding, thus inhibiting IL-1beta-induced degenerative process in NPCs through Wnt signaling. Rescuing circSEMA4B expression in NPCs in IDD might present a potential strategy for IDD improvement. |