Circular RNA derived from TIMP2 functions as a competitive endogenous RNA and regulates intervertebral disc degeneration by targeting miR?185?5p and matrix metalloproteinase 2.

ABSTRACT: Intervertebral disc degeneration (IDD) is an important cause of lower back pain, although the underlying mechanisms remain poorly understood. The present study aimed to examine the role of a circular RNA derived from tissue inhibitor of metallopeptidases 2 (circ?TIMP2) in degenerative nucleus pulposus (NP) tissues, and to validate its function in cultured human NP cells. Overexpression of miR?185?5p in NP cells markedly inhibited the enhanced extracellular matrix (ECM) catabolism induced by tumor necrosis factor?? (TNF??) and interleukin?1? (IL?1?) treatment. Bioinformatics analysis demonstrated that matrix metalloproteinase 2 (MMP2) was a potential target of miR?185?5p. MMP2 protein expression levels were increased following treatment with TNF?? and IL?1? in NP cells compared with those in untreated cells, and this effect was attenuated by transfection with miR?185?5p. Compared with normal NP tissues, IDD samples exhibited higher circ?TIMP2 expression levels. In addition, overexpression of circ?TIMP2 promoted ECM catabolism and suppressed ECM anabolism. Furthermore, circ?TIMP2 sequestered miR?185?5p, which may potentially upregulate the target genes associated with ECM degradation. In conclusion, the results of the present study revealed that circ?TIMP2 promoted TNF??? and IL?1??induced NP cell imbalance between ECM anabolism and catabolism via miR?185?5p?MMP2 signaling. These findings provide a potential therapeutic option for the treatment of IDD.

SUBMITTER: Guo W 

PROVIDER: S-EPMC7307854 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature