Role of LncRNA TUG1 in intervertebral disc degeneration and nucleus pulposus cells via regulating Wnt/β-catenin signaling pathway

Zou

J of Cellular Biochemistry

et al. 2018

Intervertebral disc (IVD) degeneration (IDD) is a major contributor to low back pain. During IDD progression, ROS can be produced in the form of H O in nucleus pulposus cells (NPCs) in response to elevated cytokines, leading to subsequent alternations of cell fate and metabolic processes. Genetic factors are considered as main contributors to IDD pathopoiesis. Herein, we investigated the detailed function and mechanism of H19, one of the most up-regulated lncRNAs in IDD specimens, in H O -induced cell senescence model in NPCs. H19 could accelerate H O -induced degenerative changes by promoting cell senescence, increasing ADAMTS-5 and MMPs protein levels and Collagen I content, as well as suppressing NPC proliferation through activating Wnt/β-catenin signaling. Moreover, miR-22, a direct target of H19, could bind to the 3'UTR of LEF1 to inhibit its expression and reverse the effect of H19 on NPCs, thus inhibiting Wnt/β-catenin signaling. Taken together, H19 acts as a ceRNA to compete with LEF1 for miR-22, thus modulating downstream Wnt/β-catenin signaling in NPCs; H19/miR-22/LEF1 might be a novel target for improving H O -induced NPC senescence and treatment for IDD.

Section: Discussionsupporting

confidence: 88%

LncRNA H19 targets miR‐22 to modulate H₂O₂‐induced deregulation in nucleus pulposus cell senescence, proliferation, and ECM synthesis through Wnt signaling

Zou

J of Cellular Biochemistry

et al. 2018

“…Accumulating studies exist with regard to the critical functions of lncRNAs in the pathogenesis of IDD. For instance, knockdown of lncRNA taurine up‐regulated gene 1 (TUG1) was found to inhibit the apoptosis and senescence and promote the proliferation of NPCs via blocking Wnt/β‐catenin pathway in IDD . LncRNA nuclear enriched abundant transcript 1 (NEAT1) contributed to ECM degradation via extracellular signal‐regulated kinase/mitogen‐activated protein kinase (ERK/MAPK) pathway activation in NPCs .…”

Section: Discussionmentioning

confidence: 99%

LINC00969 promotes the degeneration of intervertebral disk by sponging miR‐335‐3p and regulating NLRP3 inflammasome activation

Hao

et al. 2018

IUBMB Life

Long noncoding RNAs (LncRNAs) may serve as miRNA sponges to regulate the expressions of miRNA target genes. LncRNA LINC00969 has been indicated to be upregulated in intervertebral disk degeneration. However, the regulatory mechanism of LINC00969 in intervertebral disk degeneration progression remains unclear. Differently expressed LINC00969, miR‐335‐3p, and thioredoxin‐interacting protein (TXNIP) were determined in nucleus pulposus (NP) tissues and cells isolated from patients with intervertebral disk degeneration. The interaction between LINC00969, miR‐335‐3p, and TXNIP was also assessed. In this study, we demonstrated that LINC00969 was highly expressed, whereas miR‐335‐3p was aberrantly downregulated in NP tissues and cells of intervertebral disk degeneration patients. In addition, our results suggested that LINC00969 enhanced NP cell apoptosis. More importantly, LINC00969 was identified to function as a competitive endogenous RNA (ceRNA) for miR‐335‐3p to positively regulate TXNIP expression in vitro. Our study provided evidence for the cross‐talk between LINC00969, miR‐335‐3p, and TXNIP, shedding light on the therapy for intervertebral disk degeneration. © 2018 IUBMB Life, 71(5):611–618, 2019

“…For example, Wang et al found that lncRNA linc‐ADAMTS5 cooperates with RREB1 to suppress ADAMTS5 expression, then affecting ECM degeneration of the IVD. Chen et al indicated that TUG1 expression was up‐regulated in degenerated IVD tissues and positively associated with β‐catenin and Wnt expression. Inhibited expression of TUG1 inhibited the expression of β‐catenin, Bax, ADAMTS5, MMP3, Caspase‐3 and Wnt1 and promoted the COL2A1, Aggrecan and Bcl‐2 expression.…”

Section: Discussionmentioning

confidence: 99%

LncRNA‐RMRP promotes nucleus pulposus cell proliferation through regulating miR‐206 expression

J Cellular Molecular Medi

Peng

Gong

et al. 2018

Long noncoding RNAs (LncRNAs) are involved in the pathogenesis of intervertebral disc degeneration (IDD). However, the biological function and expression of RMRP were still unclear. In our study, we showed that RMRP expression was up‐regulated in degenerated NP tissues compared to normal NP samples, and higher RMRP expression was associated with the disc degeneration grade. Further studies indicated that ectopic expression of RMRP enhanced NP cell growth and also enhanced the expression of ki‐67, PCNA and cyclin D1 in the NP cell. Moreover, overexpression of RMRP promoted the expression of Type II collagen and aggrecan and suppressed the expression of MMP13 and ADAMTS4. In addition, we found that the expression of miR‐206 was down‐regulated in degenerated NP tissues compared to normal NP samples, and lower miR‐206 expression was correlated with the disc degeneration grade. Interestingly, we indicated that miR‐206 expression in NP tissues was negatively correlated with the expression of RMRP. Ectopic expression of miR‐206 suppressed NP cell proliferation and suppressed the expression of Type II collagen and aggrecan and enhanced the expression of MMP13 and ADAMTS4. Furthermore, we demonstrated that overexpression of RMRP increased NP cell growth and regulated ECM expression through targeting miR‐206. These results suggested that lncRNA‐RMRP promoted the progression of IDD through targeting miR‐206, providing an attractive new therapeutic approach for the treatment of IDD disease.