microRNA-222 targeting PTEN promotes neurite outgrowth from adult dorsal root ganglion neurons following sciatic nerve transection.
microRNA-222 targeting PTEN promotes neurite outgrowth from adult dorsal root ganglion neurons following sciatic nerve transection.
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microRNA-222 靶向 PTEN 促进坐骨神经横断后成人背根神经节神经突生长
DOI：
10.1371/journal.pone.0044768
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Ding F
中科院分区：
文献类型：
--
作者：
Zhou S;Shen D;Wang Y;Gong L;Tang X;Yu B;Gu X;Ding F
背根神经节（DRG）神经元在神经损伤后自发地经历轴突生长。microRNAs（miRNAs）是一类非编码的小分子RNA，在多种生物学过程中负调控基因的表达。然而，miRNAs在调节DRG神经元对损伤刺激的反应中的作用尚未完全了解。在此，进行微阵列分析以分析大鼠坐骨神经横断后L4-L 6 DRG中的miRNA。26个已知的miRNAs在损伤后0、1、4、7、14 d差异表达，生物信息学分析表明，miRNAs的潜在靶点与神经再生有关。在这26种miRNAs中，microRNA-222（miR-222）是我们的研究重点，因为它的表达增加促进了神经突起的生长，而miR-222抑制剂使其沉默则减少了神经突起的生长。敲除实验证实，10号染色体上缺失的磷酸酶和张力蛋白同源物（PTEN）是神经再生的主要抑制剂，是DRG神经元中miR-222的直接靶点。此外，我们发现miR-222可能通过PTEN调节cAMP反应元件结合蛋白（CREB）的磷酸化，c-Jun的激活可能增强miR-222的表达。总的来说，我们的数据表明miR-222可以通过靶向PTEN来调节背根神经节神经元的神经突生长。
Dorsal root ganglia (DRG) neurons spontaneously undergo neurite growth after nerve injury. MicroRNAs (miRNAs), as small, non-coding RNAs, negatively regulate gene expression in a variety of biological processes. The roles of miRNAs in the regulation of responses of DRG neurons to injury stimuli, however, are not fully understood. Here, microarray analysis was performed to profile the miRNAs in L4-L6 DRGs following rat sciatic nerve transection. The 26 known miRNAs were differentially expressed at 0, 1, 4, 7, 14 d post injury, and the potential targets of the miRNAs were involved in nerve regeneration, as analyzed by bioinformatics. Among the 26 miRNAs, microRNA-222 (miR-222) was our research focus because its increased expression promoted neurite outgrowth while it silencing by miR-222 inhibitor reduced neurite outgrowth. Knockdown experiments confirmed that phosphatase and tensin homolog deleted on chromosome 10 (PTEN), a major inhibitor of nerve regeneration, was a direct target of miR-222 in DRG neurons. In addition, we found that miR-222 might regulate the phosphorylation of cAMP response element binding protein (CREB) through PTEN, and c-Jun activation might enhance the miR-222 expression. Collectively, our data suggest that miR-222 could regulate neurite outgrowth from DRG neurons by targeting PTEN.
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影响因子：
25
作者：
Mellios N;Sugihara H;Castro J;Banerjee A;Le C;Kumar A;Crawford B;Strathmann J;Tropea D;Levine SS;Edbauer D;Sur M
通讯作者：
Sur M
影响因子：
2.5
作者：
Izumi, Bunichiro;Nakasa, Tomoyuki;Ochi, Mitsuo
通讯作者：
Ochi, Mitsuo
影响因子：
16.2
作者：
Gao, Y;Deng, KW;Filbin, MT
通讯作者：
Filbin, MT
影响因子：
16.2
作者：
Neumann, S;Bradke, F;Basbaum, AI
通讯作者：
Basbaum, AI
DOI：
10.1073/pnas.1015691107
发表时间：
2010-11-23
影响因子：
11.1
作者：
Magill, Stephen T.;Cambronne, Xiaolu A.;Goodman, Richard H.
通讯作者：
Goodman, Richard H.