miR-21 Promotes Human Nucleus Pulposus Cell Proliferation through PTEN/AKT Signaling |
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Authors: | Hongzhe Liu Xiangwang Huang Xiangyang Liu Sheng Xiao Yi Zhang Tiecheng Xiang Xiongjie Shen Guoping Wang Bin Sheng |
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Affiliation: | Department of Orthopedic Surgery, Hunan Provincial People’s Hospital, Changsha 10005, China; E-Mails: (H.L.); (X.L); (S.X.); (Y.Z.); (T.X.); (X.S.); (G.W.); (B.S.) |
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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 {"type":"entrez-nucleotide","attrs":{"text":"Ly294002","term_id":"1257998346","term_text":"LY294002"}}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. |
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Keywords: | disc degeneration nucleus pulposus cells miRNA miR-21 proliferation |
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