MicroRNA-10b regulates tumorigenesis in neurofibromatosis type 1

被引：78

作者：

Chai, Guolin ^{[1
]}

Liu, Ning ^{[1
]}

Ma, Junrong ^{[1
]}

Li, Hua

Oblinger, Janet L. ^{[2
,3
,4
]}

Prahalad, Agasanur K. ^{[1
]}

Gong, Meng ^{[1
]}

Chang, Long-Sheng ^{[2
,3
,4
]}

Wallace, Margaret

Muir, David ^{[5
,6
]}

Guha, Abhijit ^{[7
,8
]}

Phipps, Roger J. ^{[1
]}

Hock, Janet M. ^{[1
]}

Yu, Xijie ^{[1
]}

机构：

[1] Maine Inst Human Genet & Hlth, Bangor, ME USA

[2] Nationwide Childrens Hosp, Dept Pediat, Res Inst, Columbus, OH USA

[3] Nationwide Childrens Hosp, Dept Otolaryngol, Res Inst, Columbus, OH USA

[4] Ohio State Univ, Columbus, OH 43210 USA

[5] Univ Florida, Dept Pediat, Gainesville, FL USA

[6] Univ Florida, Dept Neurosci, Gainesville, FL 32610 USA

[7] Univ Hlth Network, Toronto Western Hosp, Alan & Susan Hudson Chair Neurooncol, Dept Surg, Toronto, ON, Canada

[8] Univ Toronto, Hosp Sick Children, Res Inst, Arthur & Sonia Labatts Brain Tumor Ctr, Toronto, ON, Canada

来源：

CANCER SCIENCE | 2010年 / 101卷 / 09期

关键词：

NERVE SHEATH TUMORS; SCHWANN-CELLS; RAS; ACTIVATION; GENE; RNA; EXPRESSION; GROWTH; NF1; RHO;

D O I：

10.1111/j.1349-7006.2010.01616.x

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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).

引用

页码：1997 / 2004

页数：8

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[1] The Ras inhibitor farnesylthiosalicylic acid as a potential therapy for neurofibromatosis type 1 [J].