miR-21 promotes human nucleus pulposus cell proliferation through PTEN/AKT signaling.
miR-21 promotes human nucleus pulposus cell proliferation through PTEN/AKT signaling.
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DOI：
10.3390/ijms15034007
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发表时间：
2014-03-05
影响因子：
5.6
通讯作者：
Sheng B
中科院分区：
文献类型：
--
作者：
Liu H;Huang X;Liu X;Xiao S;Zhang Y;Xiang T;Shen X;Wang G;Sheng B
髓核细胞增殖在椎间盘退变发病机制中的确切作用仍有待阐明。最近的研究结果表明，microRNA（一类小非编码 RNA）可能在许多病理条件下调节细胞增殖。在这里，我们发现，与从特发性脊柱侧凸患者分离的髓核组织相比，退变髓核组织中的 miR-21 显着上调，并且 miR-10b 水平与椎间盘退变程度相关。此外，生物信息学靶点预测将 PTEN 确定为 miR-21 的推定靶点。 miR-21通过直接靶向3'UTR抑制PTEN表达，并且这种抑制通过miR-21结合位点突变而消除。 miR-21 过表达刺激细胞增殖和 AKT 信号通路激活，从而导致细胞周期蛋白 D1 翻译。此外，由 miR-21 过表达诱导的增殖和细胞周期蛋白 D1 表达的增加几乎被 AKT 抑制剂 Ly294002 完全阻断。综上所述，椎间盘退变中异常的 miR-21 上调可能会靶向 PTEN，从而通过去抑制 Akt 通路导致髓核细胞异常增殖。我们的研究还强调了 miR-21 和 PTEN/Akt 通路作为椎间盘退变新治疗靶点的潜力。
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.
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