Roger J Phipps

Publications (1)3.33 Total impact

• Article: MicroRNA-10b regulates tumorigenesis in neurofibromatosis type 1.

  Guolin Chai, Ning Liu, Junrong Ma, Hua Li, Janet L Oblinger, Agasanur K Prahalad, Meng Gong, Long-Sheng Chang, Margaret Wallace, David Muir, Abhijit Guha, Roger J Phipps, Janet M Hock, Xijie Yu
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  ABSTRACT: 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 Science 09/2010; 101(9):1997-2004. · 3.33 Impact Factor