MiR-27a regulates apoptosis in nucleus pulposus cells by targeting PI3K.
MiR-27a regulates apoptosis in nucleus pulposus cells by targeting PI3K.
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DOI：
10.1371/journal.pone.0075251
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Tang X
中科院分区：
文献类型：
--
作者：
Liu G;Cao P;Chen H;Yuan W;Wang J;Tang X
细胞凋亡在椎间盘退变（IDD）发病机制中的确切作用仍有待阐明。我们分析了退变髓核（NP）细胞，发现miR-27 a的表达增加。使用实时RT-PCR进一步验证miR-27 a的过表达。生物信息学靶标预测将磷酸肌醇-3激酶（PI 3 K）鉴定为miR-27 a的推定靶标。此外，miR-27 a通过直接靶向其3 '-UTR来抑制PI 3 K表达，并且这种抑制通过miR-27 a结合位点的突变来消除。包括细胞生长、增殖、迁移和粘附的各种细胞过程通过PI 3 K/AKT信号传导途径的激活来调节，并且已知髓核细胞强烈表达磷酸化存活蛋白AKT。我们的研究结果确定PI 3 K为miR-27 a的新靶点。因此，miR-27 a的上调靶向PI 3 K，启动髓核细胞的凋亡。本研究揭示了下调miR-27 a可能通过预防髓核细胞凋亡来开发IDD治疗的新干预措施。
The precise role of apoptosis in the pathogenesis of intervertebral disc degeneration (IDD) remains to be elucidated. We analyzed degenerative nucleus pulposus (NP) cells and found that the expression of miR-27a was increased. The overexpression of miR-27a was further verified using real-time RT-PCR. Bioinformatics target prediction identified phosphoinositide-3 kinases (PI3K) as putative targets of miR-27a. Furthermore, miR-27a inhibited PI3K expression by directly targeting their 3’-UTRs, and this inhibition was abolished by mutation of the miR-27a binding sites. Various cellular processes including cell growth, proliferation, migration and adhesion are regulated by activation of the PI3K/AKT signaling pathway, and nucleus pulposus cells are known to strongly express the phosphorylated survival protein AKT. Our results identify PI3K as a novel target of miR-27a. Upregulation of miR-27a thus targets PI3K, initiating apoptosis of nucleus pulposus cells. This present study revealed that downregulated miR-27a might develop a novel intervention for IDD treatment through the prevention of apoptosis in Nucleus pulposus Cells.
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