The human RECQ1 helicase is highly expressed in glioblastoma and plays an important role in tumor cell proliferation

Abstract

BackgroundRecQ helicases play an essential role in the maintenance of genome stability. In humans, loss of RecQ helicase function is linked with predisposition to cancer and/or premature ageing. Current data show that the specific depletion of the human RECQ1 helicase leads to mitotic catastrophe in cancer cells and inhibition of tumor growth in mice.ResultsHere, we show that RECQ1 is highly expressed in various types of solid tumors. However, only in the case of brain gliomas, the high expression of RECQ1 in glioblastoma tissues is paralleled by a lower expression in the control samples due to the poor expression of RECQ1 in non-dividing tissues. This conclusion is validated by immunohistochemical analysis of a tissue microarray containing 63 primary glioblastomas and 19 perilesional tissue samples, as control. We also show that acute 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 U-87 glioblastoma cells. Moreover, RECQ1 depleted T98G and U-87 cells are hypersensitive to HU or temozolomide treatment.ConclusionsCollectively, these results indicate that RECQ1 has a unique and important role in the maintenance of genome integrity. Our results also suggest that RECQ1 might represent a new suitable target for anti cancer therapies aimed to arrest cell proliferation in brain gliomas.

RECQ1 is required for cellular resistance to replication stress and catalyzes strand exchange on stalled replication fork structures

“…8). Consistently, downregulation of RECQ1 was shown to trigger spontaneous Rad51 foci formation and an increase in SCEs, 35,36 and this is also consistent with the finding that RECQ1 mouse embryonic fibroblasts (MEFs) are associated with chromosomal instability and an increase in the frequency of SCEs. 51 HR-mediated repair of broken replication forks can particularly result in the blockage of leading-strand extensions in the presence of bulky lesions.…”

“…Our results are consistent with the previous observations that transient depletion of RECQ1 affected cell proliferation. [34][35][36][37] Next, we wanted to analyze the sensitivity patterns of RECQ1 depletion. Using the two independent lentiviral shRNA constructs, depletion of RECQ1 was performed in both HeLa (Fig.…”

Association between RECQL5 genetic polymorphisms and susceptibility to breast cancer

“…As described previously, RECQ helicases comprise a highly conserved family of DNA helicases that operate to maintain genomic DNA stability in humans [20]. Defects in human RECQ helicases are associated with premature aging, genome instability, and cancer predisposition [21].…”

Development of Gene Expression–Based Score to Predict Sensitivity of Multiple Myeloma Cells to DNA Methylation Inhibitors

“…RECQ1 silencing in cancer cells resulted in mitotic catastrophe and injection of siRNA targeting RECQ1 prevented tumor growth in murine models (54)(55)(56). More recently, it was shown that RECQ1 is highly expressed in various types of solid tumors including colon carcinoma, thyroid cancer, lung cancer, and brain glioblastoma tissues (57). In glioblastoma cell lines, depletion of RECQ1 by RNA interference results in a significant reduction of cellular proliferation, perturbation of S-phase progression, spontaneous g-H2AX foci formation, and hypersensitivity to hydroxyurea and temozolomide treatments (57).…”