Involvement of DDX6 gene in radio- and chemoresistance in glioblastoma.

ABSTRACT

CCRT (concomitant chemotherapy and radiation therapy) is often used for glioblastoma multiforme (GBM) treatment after surgical therapy, however, patients treated with CCRT undergo poor prognosis due to development of treatment resistant recurrence. Many studies have been performed to overcome these problems and to discover genes influencing treatment resistance. To discover potential genes inducing CCRT resistance in GBM, we used whole genome screening by infecting shRNA pool in patient-derived cell. The cells infected ~8,000 shRNAs were implanted in mouse brain and treated RT/TMZ as in CCRT treated patients. We found DDX6 as the candidate gene for treatment resistance after screening and establishing DDX6 knock down cells for functional validation. Using these cells, we confirmed tumor associated ability of DDX6 in vitro and in vivo. Although proliferation improvement was not found, decreased DDX6 influenced upregulated clonogenic ability and resistant response against radiation treatment in vivo and in vitro. Taken together, we suggest that DDX6 discovered by using whole genome screening was responsible for radio- and chemoresistance in GBM.