LncRNA TUG1 promotes the intervertebral disc degeneration and nucleus pulposus cell apoptosis though modulating miR-26a/HMGB1 axis and regulating NF-kappa B activation

Tang, Ning1; Dong, Yulei1; Xiao, Tinghui2; Zhao, Hong1

2020

American Journal of Translational Research   影响因子和分区

1943-8141

Aims: This study was to investigate the effect of TUG1 on apoptosis and ECM degradation of human degenerative intervertebral disc nucleus pulposus cells (NPCs) and its mechanism. Methods: Human degenerative intervertebral disc NP tissues were obtained from 10 patients with lumbar disc herniation (LDH) who underwent lumbar spine surgery (IDD group), normal intervertebral disc NP tissues were obtained from 10 patients with lumbar vertebrae fractures (LVF group). Results: The expression of TUG1 and HMGB1 protein in human degenerative disc NP tissues and NPCs was significantly increased, while the level of miR-26a was significantly decreased. Overexpression of TUG1 inhibited the proliferation while promoted apoptosis and ECM degradation of human degenerative intervertebral disc NPCs. Simultaneously, the effect of TUG1 knockdown on NPCs was opposite. Interestingly, TUG1 acted as an endogenous sponge to down-regulate the expression of miR-26a in NPCs by direct binding to miR26a. Overexpression of miR-26a reversed the effects of TUG1 overexpression on apoptosis and ECM degradation. Additionally, HMGB1 was a target gene of miR-26a. The increased expression of HMGB1 induced by TUG1 overexpression could be reversed by the introduction of miR-26a mimic. Overexpression of TUG1 significantly upregulated the expression of p65 in the nucleus, while overexpression of TUG1 partially abolished the inhibition of NF-kappa B by QNZ pretreatment. Conclusion: TUG1 could promote the apoptosis and ECM degradation of degenerated intervertebral disc NPCs by regulating the miR-26a/HMGB1, which may be involved in the activation of NF-kappa B pathway.

Intervertebral disc degeneration nucleus pulposus cells long-chain non-coding RNAs taurine upregulated gene 1 apoptosis extracellular matrix degradation

SCI

英语

其他

Oncology ; Research & Experimental Medicine

Oncology ; Medicine, Research & Experimental

WOS:000576802600009

E-CENTURY PUBLISHING CORP

Web of Science

1.Chinese Acad Med Sci, Peking Union Med Coll Hosp, Dept Orthoped, 1 Shuaifuyuan, Beijing 100730, Peoples R China
2.Southern Univ Sci & Technol, Affiliated Hosp 1, Shenzhen Peoples Hosp, Dept Orthoped, Shenzhen, Peoples R China

Tang, Ning,Dong, Yulei,Xiao, Tinghui,et al. LncRNA TUG1 promotes the intervertebral disc degeneration and nucleus pulposus cell apoptosis though modulating miR-26a/HMGB1 axis and regulating NF-kappa B activation[J]. American Journal of Translational Research,2020,12(9):5449-+.

Tang, Ning,Dong, Yulei,Xiao, Tinghui,&Zhao, Hong.(2020).LncRNA TUG1 promotes the intervertebral disc degeneration and nucleus pulposus cell apoptosis though modulating miR-26a/HMGB1 axis and regulating NF-kappa B activation.American Journal of Translational Research,12(9),5449-+.

Tang, Ning,et al."LncRNA TUG1 promotes the intervertebral disc degeneration and nucleus pulposus cell apoptosis though modulating miR-26a/HMGB1 axis and regulating NF-kappa B activation".American Journal of Translational Research 12.9(2020):5449-+.