PRAF2 stimulates cell proliferation and migration and predicts poor prognosis in neuroblastoma

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.

Transcriptional variations in the wider peritumoral tissue environment of pancreatic cancer

“…It induces apoptotic cell death upon expression and is counteracted by Bcl‐xL . It stimulates cell proliferation and migration and predicts poor prognosis in neuroblastoma and glioma . In a genome‐wide siRNA screen aiming at the identification of new genes involved in autophagy, PRAF2 was found as a gene mediating autophagy .…”

“…40 It stimulates cell proliferation and migration and predicts poor prognosis in neuroblastoma and glioma. 41,42 In a genome-wide siRNA screen aiming at the identification of new genes involved in autophagy, PRAF2 was found as a gene mediating autophagy. 43 PLK4 (Polo-like kinase 4) is a conserved upstream regulator of centriole duplication.…”

Anatomical and ultrastructural study of PRAF2 expression in the mouse central nervous system

“…PRAF2 might control Bcl-xl and Bax localization in the RE or mitochondria of midbrain neurons, the impaired sorting of these proteins potentially leading to neurodegeneration or neural death after brain injury. PRAF2-dependent perturbation of the pro and anti-apoptotic equilibrium, trough BAX and Bcl-xL relocation, might play a role in cancer genesis or progression (Borsics et al 2010;Fo et al 2006;Geerts et al 2007;Vento et al 2010;Yco et al 2013).…”

“…For several years, no clear biological function was attributed to PRAF2, except its overexpression in multiple cancers (Borsics et al 2010;Fo et al 2006;Vento et al 2010;Yco et al 2013). Recently, PRAF2 was reported to interact with GB1, the ligand-binding subunit of the GABA B receptor (Doly et al 2015).…”

“…Changes of PRAF2 concentration were documented during embryonic neuronal growth in culture (Doly et al 2015), in human nervous system cancers (Borsics et al 2010;Geerts et al 2007;Vento et al 2010;Yco et al 2013) or in case of chronic alcohol intake (Enoch et al 2013). Because of the prominent regulatory effects of PRAF2 on GABA B function and the multiple roles of this receptor in the CNS, a precise analysis of PRAF2 distribution relative to that of GABA B subunits is of major interest.…”