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MicroRNA-10b regulates tumorigenesis in neurofibromatosis type 1
- Source :
- Cancer science. 101(9)
- Publication Year :
- 2010
-
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.
- Subjects :
- congenital, hereditary, and neonatal diseases and abnormalities
Cancer Research
Pathology
medicine.medical_specialty
Neurofibromatosis 1
Cell Survival
Blotting, Western
Biology
medicine.disease_cause
RNA interference
Cell Movement
Cell Line, Tumor
microRNA
medicine
Tumor Cells, Cultured
Gene silencing
Humans
RNA, Antisense
Neurofibromatosis
Phosphorylation
Extracellular Signal-Regulated MAP Kinases
3' Untranslated Regions
Cell Proliferation
Oligonucleotide Array Sequence Analysis
Neurofibromin 1
Reverse Transcriptase Polymerase Chain Reaction
Gene Expression Profiling
HEK 293 cells
General Medicine
medicine.disease
nervous system diseases
Gene Expression Regulation, Neoplastic
MicroRNAs
HEK293 Cells
Oncology
biology.protein
Cancer research
ras Proteins
Schwann Cells
Signal transduction
Carcinogenesis
Signal Transduction
Subjects
Details
- ISSN :
- 13497006
- Volume :
- 101
- Issue :
- 9
- Database :
- OpenAIRE
- Journal :
- Cancer science
- Accession number :
- edsair.doi.dedup.....b1e4e38ed4b3e9e1a40cb634aea53f6f