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MicroRNA-204 critically regulates carcinogenesis in malignant peripheral nerve sheath tumors
- Publication Year :
- 2012
- Publisher :
- Oxford University Press, 2012.
-
Abstract
- Malignant peripheral nerve sheath tumors (MPNSTs) are highly aggressive soft tissue sarcomas accounting for 3%–10% of all soft tissue sarcomas. Neurofibromatosis type 1 (NF1) is the most important known risk factor. MPNSTs are often diagnosed at an advanced stage when distant metastases have developed. Although surgical resection remains the main treatment for MPNSTs, complete surgical resection is rarely possible. The prognosis for patients with MPNSTs is poor. There is an urgent need for improved therapies. To this end, we investigated whether microRNA (miR), specifically miR-204, might be implicated in MPNSTs because it is located at a cancer-associated genomic region exhibiting high frequency of loss of heterozygosity in tumors. We show that miR-204 expression is downregulated in NF1 and non-NF1 MPNST tumor tissues and in tumor cell lines. Restoring miR-204 expression in MPNST cell lines STS26T (non-NF1), ST88-14 (NF1), and T265p21 (NF1) significantly reduces cellular proliferation, migration, and invasion in vitro. Restoring miR-204 expression in STS26T decreases tumor growth and malignant progression in vivo. We also report that miR-204 inhibits Ras signaling and expression of high mobility group gene A2. These findings support the hypothesis that miR-204 plays critical roles in MPNST development and tumor progression. miR-204 may represent a novel biomarker for diagnosis and a candidate target with which to develop effective therapies for MPNSTs.
- Subjects :
- Male
Cancer Research
Pathology
medicine.medical_specialty
Blotting, Western
Transplantation, Heterologous
Mice, SCID
Biology
medicine.disease_cause
Nerve Sheath Neoplasms
Loss of heterozygosity
Mice
Mice, Inbred NOD
microRNA
medicine
Animals
Humans
Neoplasm Invasiveness
Neurofibromatosis
Cell Proliferation
Oligonucleotide Array Sequence Analysis
Reverse Transcriptase Polymerase Chain Reaction
medicine.disease
Transplantation
MicroRNAs
Cell Transformation, Neoplastic
Oncology
Tumor progression
Basic and Translational Investigations
Cancer research
Biomarker (medicine)
Neurology (clinical)
Carcinogenesis
Nerve sheath neoplasm
Signal Transduction
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....7543400a7975b942531c9ee274adf227