Spine Surgery, The Third Affiliated Hospital of Soochow University, No. 185 Juqian Street, Changzhou, Jiangsu 213003, China.
Biomed Res Int. 2017;2017:5251236. doi: 10.1155/2017/5251236. Epub 2017 Sep 12.
Yes-associated protein (YAP) is proved to increase miR-29a in the present study, but the relevant molecular mechanism is not clear. Also, growing evidence indicates that the high-level miR-29a promotes the neurite outgrowth by decreasing PTEN (phosphatase and tensin homologue deleted on chromosome 10). Results show that the expression of miR-29a increases but the PTEN decreases during transfecting the N2a cells with the YAP plasmid. Meanwhile, the advancement of neurite outgrowth is presented via using multiple methods to detect the expression of GAP-43 and NF-200, which have a strong association with neurite outgrowth. The expression of miR-29a, GAP-43, and NF-200 shows an opposite tendency compared to the PTEN when YAP is downregulated. By treating N2a cells with miR-29a mimic and inhibitor, we also find the same conclusion. For in silico analysis of miR-29a, its promoter may have a binding site for YAP. Based on a luciferase reporter assay and a chromatin immunoprecipitation (ChIP) experiment, we demonstrate that YAP could increase the expression of miR-29a by targeting the promoter of miR-29a. In conclusion, the results identify that YAP promotes the neurite outgrowth via targeting the promoter of miR-29a, and it may be an effective therapeutic medicine for the neural disease.
Yes 相关蛋白（YAP）在本研究中被证明可以增加 miR-29a，但相关的分子机制尚不清楚。此外，越来越多的证据表明，高水平的 miR-29a 通过降低 PTEN（第 10 号染色体缺失的磷酸酶和张力蛋白同源物）来促进轴突生长。结果表明，在转染 YAP 质粒的 N2a 细胞中，miR-29a 的表达增加，但 PTEN 减少。同时，通过使用多种方法检测与轴突生长密切相关的 GAP-43 和 NF-200 的表达，显示出轴突生长的进展。当 YAP 被下调时，miR-29a、GAP-43 和 NF-200 的表达与 PTEN 呈相反趋势。通过用 miR-29a 模拟物和抑制剂处理 N2a 细胞，我们也得出了相同的结论。对 miR-29a 的计算机分析表明，其启动子可能有 YAP 的结合位点。基于荧光素酶报告基因检测和染色质免疫沉淀（ChIP）实验，我们证明 YAP 可以通过靶向 miR-29a 的启动子来增加 miR-29a 的表达。总之，这些结果表明 YAP 通过靶向 miR-29a 的启动子促进轴突生长，它可能是治疗神经疾病的有效药物。
