MicroRNA-10b regulates tumorigenesis in neurofibromatosis type 1.
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.
Chai
Guolin
G
Maine Institute for Human Genetics & Health, Bangor, Maine.
Liu
Ning
N
Ma
Junrong
J
Li
Hua
H
Oblinger
Janet L
JL
Prahalad
Agasanur K
AK
Gong
Meng
M
Chang
Long-Sheng
LS
Wallace
Margaret
M
Muir
David
D
Guha
Abhijit
A
Phipps
Roger J
RJ
Hock
Janet M
JM
Yu
Xijie
X
D020413:3' Untranslated Regions / Q000235:genetics; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002470:Cell Survival; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D009456:Neurofibromatosis 1 / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D025542:Neurofibromin 1 / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010766:Phosphorylation; D016372:RNA, Antisense / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012583:Schwann Cells / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D018631:ras Proteins / Q000235:genetics* / Q000378:metabolism
D020413:3' Untranslated Regions; C547183:MIRN10 microRNA, human; D035683:MicroRNAs; D025542:Neurofibromin 1; D016372:RNA, Antisense; D048049:Extracellular Signal-Regulated MAP Kinases; D018631:ras Proteins