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Research Abstracts Online
January 2009 - March 2010

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University of Minnesota Twin Cities
Medical School
Department of Laboratory Medicine and Pathlogy

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. The goal is to achieve a better understanding of the etiology and progression of MPNST, as well as to have identified potential miRNA biomarkers for malignant transformation and to have begun to define mi-RNA-mRNA interactions.

Group Members

Rasik Phalak, Graduate Student
Aaron Sarver, Research Associate
Venugopal Thayanithy, Research Associate