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Int. J. Mol. Sci. 2014, 15(3), 4007-4018; doi:10.3390/ijms15034007
Article

miR-21 Promotes Human Nucleus Pulposus Cell Proliferation through PTEN/AKT Signaling

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Received: 24 November 2013; in revised form: 16 January 2014 / Accepted: 26 January 2014 / Published: 5 March 2014
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
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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 disc degeneration; nucleus pulposus cells; miRNA; miR-21; proliferation
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

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.

AMA Style

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.

Chicago/Turabian Style

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.


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