Research Abstracts Online
2008 - March 2009
University of Minnesota Twin Cities
Department of Laboratory Medicine and Pathology
PI: Subbaya Subramanian
Roles of MicroRNAs in Malignant Transformation of Peripheral Nerve Sheath Tumor
Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive soft tissue tumors that occur either sporadically or in patients with neurofibromatosis. Malignant transformation of the benign neurofibroma to MPNST is incompletely understood at the molecular level. Preliminary genome-wide gene expression and microRNA (miRNA) profiling studies in a series of peripheral nerve sheath tumors identified unique expression signature for the benign and malignant tumors. These researchers found p53 inactivation and significant downregulation of several miRNAs including miR-34a (a direct transcriptional target of p53) in majority of MPNSTs compared to neurofibromas. They hypothesize that microRNAs regulated by p53 play a major role in the malignant transformation of peripheral nerve sheath tumors.
To test their hypothesis, the researchers are defining profiles of MPNST susceptibility based on miRNA expression signature and defining regulatory pathways mediated by miR-34a that are etiologically significant for MPNSTs, then validating in vitro using cell lines to understand the malignant transformation process.
In a previous project, the researchers investigated whether miRNA-mRNA interactions play a central role in the onset of tumor formation and progression in Ewing’s sarcoma.
Lei Li, Research Associate