The human recq1 helicase is highly expressed in glioblastoma and plays an important role in tumor cell proliferation

Abstract

RecQ helicases play an essential role in the maintenance of genome stability. In humans, loss of RecQ helicase function is linked to predisposition to cancer and premature ageing. Distinct molecular functions for the five human RecQ helicases, and RECQ1 in particular, in replication stress and cancer remain to be defined. Within the GLIOMA project we are studying the expression and the role of RECQ1 in replication stress response and repair in glioblastoma and Glioma Stem Cells (GSC). Different papers show that GSCs play an important role in the initiation, aggressiveness and recurrence of glioblastoma. Here, we show that RECQ1 is highly expressed in various types of solid tumours, but only in the case of glioblastoma, the expression of RECQ1 is significantly increased in tumoural tissue relative to the surrounding perilesional. We also show that the depletion of RECQ1 by RNAi results in a significant reduction of cellular proliferation, perturbation of S-phase progression, and spontaneous γ-H2AX foci formation in T98G and U87 glioblastoma cells. Moreover, RECQ1 depleted cells are hypersensitive to hydroxyurea or temozolomide treatment. Collectively, these results indicate that RECQ1 has an important role in the maintenance of genome integrity and might represent a new suitable target for anti cancer therapies aimed to arrest cell proliferation in glioma. In the framework of GLIOMA project we are also working to establish a zebrafish cancer model to characterize the role of RECQ1 in glioblastoma formation and progression in vivo.