Open AccessMicroRNA‐10b regulates tumorigenesis in neurofibromatosis type 1
Author(s) -
Chai Guolin,
Liu Ning,
Ma Junrong,
Li Hua,
Oblinger Janet L.,
Prahalad Agasanur K.,
Gong Meng,
Chang LongSheng,
Wallace Margaret,
Muir David,
Guha Abhijit,
Phipps Roger J.,
Hock Janet M.,
Yu Xijie
Publication year - 2010
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2010.01616.x
Subject(s) - neurofibromin 1 , neurofibromatosis , carcinogenesis , microrna , cancer research , malignant peripheral nerve sheath tumor , biology , cell culture , cell growth , neurofibromatosis type i , microbiology and biotechnology , cancer , genetics , gene
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)