RECQ1 Helicase Silencing Decreases the Tumour Growth Rate of U87 Glioblastoma Cell Xenografts in Zebrafish Embryos

Abstract

RECQ1 helicase has multiple roles in DNA replication, including restoration of the replication fork and DNA repair, and plays an important role in tumour progression. Its expression is highly elevated in glioblastoma as compared to healthy brain tissue. We studied the effects of small hairpin RNA (shRNA)-induced silencing of RECQ1 helicase on the increase in cell number and the invasion of U87 glioblastoma cells. RECQ1 silencing reduced the rate of increase in the number of U87 cells by 30%. This corresponded with a 40% reduction of the percentage of cells in the G2 phase of the cell cycle, and an accumulation of cells in the G1 phase. These effects were confirmed in vivo, in the brain of zebrafish (Danio rerio) embryos, by implanting DsRed-labelled RECQ1 helicase-silenced and control U87 cells. The growth of resulting tumours was quantified by monitoring the increase in xenograft fluorescence intensity during a three-day period with fluorescence microscopy. The reduced rate of tumour growth, by approximately 30% in RECQ1 helicase-silenced cells, was in line with in vitro measurements of the increase in cell number upon RECQ1 helicase silencing. However, RECQ1 helicase silencing did not affect invasive behaviour of U87 cells in the zebrafish brain. This is the first in vivo confirmation that RECQ1 helicase is a promising molecular target in the treatment of glioblastoma.

Identification of a Prognostic Signature Associated With DNA Repair Genes in Ovarian Cancer

“…RECQL is involved in various types of DNA repair, including mismatch repair, NER, and direct repair. RECQL has been found to be overexpressed in many other tumors and plays a critical role in malignant progression and PARPi resistance and may serve as a potential prognostic or predictive factor for ovarian cancer (Li et al, 2016; Vittori et al, 2017; Viziteu et al, 2017). DMC1 has been reported to be an essential recombinase for meiotic homologous recombination and plays an important role in generating the diversity of genetic information.…”

Zebrafish Models of Cancer—New Insights on Modeling Human Cancer in a Non-Mammalian Vertebrate

“…Many of the following studies use seemingly unrelated types of cancer cell lines, however, the authors are usually trying to find correlations between in vitro and in vivo invasion abilities and general pathogenesis as well as the potential of cancer cells to metastasize in vivo. In the last decade, the most commonly studied types of solid tumors in zebrafish are melanoma [152], breast, prostate, colon, and pancreatic cancers [153] and glioblastoma [154]. Here, we will walk through the course of time and illustrate on the diversity of xenograft studies how zebrafish contributed to our understanding of tumorigenesis and helped to describe new potential therapeutics.…”

“…Zebrafish as a model for retinoblastoma [170] and glioblastoma [154,171,172,173,174] has been popular in the last couple of years. Many of these studies highlight the significance of zebrafish in finding novel treatment targets and evaluating cancer inhibitor efficacy in vivo.…”

RECQ1 Helicase in Genomic Stability and Cancer

“…Silencing RECQ1 in cancer cells induces cell death by mitotic catastrophe [ 60 ] and reduced tumor growth in mouse models [ 61 ]. Furthermore, using zebrafish as a model organism, a recent study demonstrated that silencing RECQ1 reduces the tumor growth rate of glioblastoma cells, U87 [ 62 ]. Transient depletion of RECQ1 using siRNA decreases cancer cell migration and invasion in breast cancer MDA-MB-231 cells by regulating the expression of genes associated with cancer progression [ 41 , 42 ].…”