Regulation of SLD5 gene expression by miR-370 during acute growth of cancer cells

SLD5 is a member of the GINS complex, essential for DNA replication in eukaryotes. It has been reported that SLD5 is involved in early embryogenesis in the mouse and cell cycle progression and genome integrity in Drosophila. SLD5 may be involved in malignant tumor progression, but its relevance in h...

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Bibliographic Details
Published in:Scientific reports 2016-08, Vol.6 (1), p.30941-30941, Article 30941
Main Authors: Yamane, Keitaro, Naito, Hisamichi, Wakabayashi, Taku, Yoshida, Hironori, Muramatsu, Fumitaka, Iba, Tomohiro, Kidoya, Hiroyasu, Takakura, Nobuyuki
Format: Article
Language:English
Subjects:
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631/80/83
Bladder cancer
Cancer
Cell cycle
Deoxyribonucleic acid
DNA
DNA biosynthesis
DNA methyltransferase
DNMT1 protein
Embryogenesis
Embryonic growth stage
Gene expression
Genomes
Humanities and Social Sciences
Interleukin 6
miRNA
multidisciplinary
Science
siRNA
Urinary bladder
Xenografts
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Summary:SLD5 is a member of the GINS complex, essential for DNA replication in eukaryotes. It has been reported that SLD5 is involved in early embryogenesis in the mouse and cell cycle progression and genome integrity in Drosophila. SLD5 may be involved in malignant tumor progression, but its relevance in human cancer has not been determined. Here, we found strong SLD5 expression in both human bladder cancer tissues from patients and cell lines. Knockdown of SLD5 using small interfering RNA resulted in reduction of cell growth both in vitro and an in vivo xenograft model. Moreover, we found that high levels of SLD5 in bladder cancer cells result from downregulation of microRNA (miR)-370 that otherwise suppresses its expression. High level expression of DNA-methyltransferase (DNMT) 1 and IL-6 were also observed in bladder cancer cells. Knockdown of IL-6 led to downregulation of DNMT1 and SLD5 expression, suggesting that IL-6-induced overexpression of DNMT1 suppresses miR-370, resulting in high SLD5 expression. Our findings could contribute to understanding tumorigenic processes and progression of human bladder cancer, whereby inhibition of SLD5 could represent a novel strategy to prevent tumor growth.
ISSN:2045-2322
2045-2322
DOI:10.1038/srep30941