title: MicroRNA-10b regulates tumorigenesis in neurofibromatosis type 1.
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.
authors.affiliation: Maine Institute for Human Genetics & Health, Bangor, Maine.
authors.forename: Guolin
authors.initials: G
authors.lastname: Chai
authors.forename: Ning
authors.initials: N
authors.lastname: Liu
authors.forename: Junrong
authors.initials: J
authors.lastname: Ma
authors.forename: Hua
authors.initials: H
authors.lastname: Li
authors.forename: Janet L
authors.initials: JL
authors.lastname: Oblinger
authors.forename: Agasanur K
authors.initials: AK
authors.lastname: Prahalad
authors.forename: Meng
authors.initials: M
authors.lastname: Gong
authors.forename: Long-Sheng
authors.initials: LS
authors.lastname: Chang
authors.forename: Margaret
authors.initials: M
authors.lastname: Wallace
authors.forename: David
authors.initials: D
authors.lastname: Muir
authors.forename: Abhijit
authors.initials: A
authors.lastname: Guha
authors.forename: Roger J
authors.initials: RJ
authors.lastname: Phipps
authors.forename: Janet M
authors.initials: JM
authors.lastname: Hock
authors.forename: Xijie
authors.initials: X
authors.lastname: Yu
mesh_terms: 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
chemical_list: 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