Abstract: The precise role of nucleus pulposus cell proliferation in the pathogenesis of intervertebral disc degeneration remains to be elucidated. Recent findings have revealed that microRNAs, a class of small noncoding RNAs, may regulate cell proliferation in many pathological conditions. Here, we showed that miR-21 was significantly upregulated in degenerative nucleus pulposus tissues when compared with nucleus pulposus tissues that were isolated from patients with idiopathic scoliosis and that miR-10b levels were associated with disc degeneration grade. Moreover, bioinformatics target prediction identified PTEN as a putative target of miR-21. miR-21 inhibited PTEN expression by directly targeting the 3'UTR, and this inhibition was abolished through miR-21 binding site mutations. miR-21 overexpression stimulated cell proliferation and AKT signaling pathway activation, which led to cyclin D1 translation. Additionally, the increase in proliferation and cyclin D1 expression induced by miR-21 overexpression was almost completely blocked by Ly294002, an AKT inhibitor. Taken together, aberrant miR-21 upregulation in intervertebral disc degeneration could target PTEN, which would contribute to abnormal nucleus pulposus cell proliferation through derepressing the Akt pathway. Our study also underscores the potential of miR-21 and the PTEN/Akt pathway as novel therapeutic targets in intervertebral disc degeneration.
Keywords: disc degeneration; nucleus pulposus cells; miRNA; miR-21; proliferation
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Liu, H.; Huang, X.; Liu, X.; Xiao, S.; Zhang, Y.; Xiang, T.; Shen, X.; Wang, G.; Sheng, B. miR-21 Promotes Human Nucleus Pulposus Cell Proliferation through PTEN/AKT Signaling. Int. J. Mol. Sci. 2014, 15, 4007-4018.
Liu H, Huang X, Liu X, Xiao S, Zhang Y, Xiang T, Shen X, Wang G, Sheng B. miR-21 Promotes Human Nucleus Pulposus Cell Proliferation through PTEN/AKT Signaling. International Journal of Molecular Sciences. 2014; 15(3):4007-4018.
Liu, Hongzhe; Huang, Xiangwang; Liu, Xiangyang; Xiao, Sheng; Zhang, Yi; Xiang, Tiecheng; Shen, Xiongjie; Wang, Guoping; Sheng, Bin. 2014. "miR-21 Promotes Human Nucleus Pulposus Cell Proliferation through PTEN/AKT Signaling." Int. J. Mol. Sci. 15, no. 3: 4007-4018.