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Genes 2017, 8(9), 222; doi:10.3390/genes8090222

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

1
Department of Genetic Toxicology and Cancer Biology, National Institute of Biology, Večna pot 111, 1000 Ljubljana, Slovenia
2
Department of Biology, Biotechnical Faculty, University of Ljubljana, Večna pot 111, 1000 Ljubljana, Slovenia
3
International Postgraduate School Jozef Stefan, Jamova 39, 1000 Ljubljana, Slovenia
4
Structural Biology Laboratory, Elettra-Sincrotrone Trieste, Strada Statale 14‑km 163, 5, Basovizza, 34149 Trieste, Italy
5
Department of Biochemistry, Faculty of Chemistry and Chemical Engineering, University of Ljubljana, Večna pot 113, 1000 Ljubljana, Slovenia
*
Author to whom correspondence should be addressed.
Academic Editor: Laura Sánchez
Received: 14 July 2017 / Revised: 18 August 2017 / Accepted: 5 September 2017 / Published: 6 September 2017
(This article belongs to the Special Issue Zebrafish: The Key for Cancer Treatment)
View Full-Text   |   Download PDF [2738 KB, uploaded 6 September 2017]   |  

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. View Full-Text
Keywords: cancer; cell cycle; DNA damage; intravital imaging; RNA interference; theranostics cancer; cell cycle; DNA damage; intravital imaging; RNA interference; theranostics
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Vittori, M.; Breznik, B.; Hrovat, K.; Kenig, S.; Lah, T.T. RECQ1 Helicase Silencing Decreases the Tumour Growth Rate of U87 Glioblastoma Cell Xenografts in Zebrafish Embryos. Genes 2017, 8, 222.

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