MicroRNA-10b regulates tumorigenesis in neurofibromatosis type 1
MicroRNA-10b regulates tumorigenesis in neurofibromatosis type 1
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DOI：
10.1111/j.1349-7006.2010.01616.x
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发表时间：
2010-09-01
期刊：
影响因子：
5.7
通讯作者：
Yu, Xijie
中科院分区：
文献类型：
--
作者：
Chai, Guolin;Liu, Ning;Yu, Xijie
microRNAs（miRNAs）在人类肿瘤中经常被失调，并在肿瘤的发生和发展中发挥重要作用。miRNAs在1型神经纤维瘤病（NF 1）肿瘤发生中的病理作用在很大程度上是未知的。我们证明了miR-10 b在分离自NF 1神经纤维瘤的原代雪旺细胞中以及在恶性外周神经鞘瘤（MPNSTs）的细胞系和肿瘤组织中上调。有趣的是，在神经外胚层细胞系：尤文肉瘤SK-ES-1细胞中发现了与低神经纤维蛋白表达相关的显著高水平的miR-10 b。反义抑制NF 1 MPNST细胞中的miR-10 b降低细胞增殖、迁移和侵袭。此外，我们发现NF 1 mRNA是miR-10 b的靶点。miR-10 b在293 T细胞中的过表达抑制了神经纤维蛋白的表达并激活了RAS信号。反义抑制miR-10 b恢复了SK-ES-1细胞中神经纤维蛋白的表达，并降低了NF 1 MPNST细胞中不依赖于神经纤维蛋白的RAS信号传导。这些结果表明，miR-10 b可能通过靶向神经纤维蛋白和RAS信号在NF 1肿瘤发生中发挥重要作用。（Cancer Sci 2010）。
MicroRNAs (miRNAs) are frequently deregulated in human tumors, and play important roles in tumor development and progression. The pathological roles of miRNAs in neurofibromatosis type 1 (NF1) tumorigenesis are largely unknown. We demonstrated that miR-10b was up-regulated in primary Schwann cells isolated from NF1 neurofibromas and in cell lines and tumor tissues from malignant peripheral nerve sheath tumors (MPNSTs). Intriguingly, a significantly high level of miR-10b correlated with low neurofibromin expression was found in a neuroectodermal cell line: Ewing's sarcoma SK-ES-1 cells. Antisense inhibiting miR-10b in NF1 MPNST cells reduced cell proliferation, migration and invasion. Furthermore, we showed that NF1 mRNA was the target for miR-10b. Overexpression of miR-10b in 293T cells suppressed neurofibromin expression and activated RAS signaling. Antisense inhibition of miR-10b restored neurofibromin expression in SK-ES-1 cells, and decreased RAS signaling independent of neurofibromin in NF1 MPNST cells. These results suggest that miR-10b may play an important role in NF1 tumorigenesis through targeting neurofibromin and RAS signaling. (Cancer Sci 2010).