101. MicroRNA-10b regulates tumorigenesis in neurofibromatosis type 1
- Author
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Meng Gong, Long-Sheng Chang, Agasanur K. Prahalad, Janet L. Oblinger, Junrong Ma, Roger J. Phipps, Hua Li, Xijie Yu, Abhijit Guha, Guolin Chai, Janet M. Hock, Ning Liu, Margaret R. Wallace, and David Muir
- 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 - 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.
- Published
- 2010