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CircSEMA4B targets miR-431 modulating IL-1beta-induced degradative changes in nucleus pulposus cells in intervertebral disc degeneration via Wnt pathway

TitleCircSEMA4B targets miR-431 modulating IL-1beta-induced degradative changes in nucleus pulposus cells in intervertebral disc degeneration via Wnt pathway
Publication TypeJournal Article
Year of Publication2018
AuthorsWang, X, Wang, B, Zou, M, Li, J, Lu, G, Zhang, Q, Liu, F, Lu, C
JournalBiochim Biophys Acta Mol Basis Dis
Volume1864
Pagination3754-3768
Date PublishedNov
ISBN Number0925-4439
Accession Number30251693
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.