Abstract
Prenylated Rab acceptor 1 domain family, member 2 (PRAF2) is a novel 19-kDa protein with four transmembrane-spanning domains that belongs to the PRAF protein family. Neuroblastoma (NB) is the most common malignant extracranial solid tumor of childhood that originates in primitive cells of the developing sympathetic nervous system. We investigated the correlation of PRAF2 mRNA expression to NB clinical and genetic parameters using Affymetrix expression analysis of a series of 88 NB tumors and examined the functional role of PRAF2 in an NB cell line using RNA interference. We found that high PRAF2 expression is significantly correlated to several unfavorable NB characteristics: MYCN amplification, high age at diagnosis, poor outcome and high INSS stage. The shRNA-mediated PRAF2 downregulation in the SK-N-SH NB cell line resulted in decreased cellular proliferation, migration and matrix-attachment. These findings were confirmed in NB patient tumor samples, where high PRAF2 expression is significantly correlated to bone and bone marrow metastasis, the main cause of death in NB patients. The present study shows that PRAF2 plays an essential role in NB tumorigenesis and metastasis.
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