LINE-1 ORF1 Protein Is Up-regulated by Reactive Oxygen Species and Associated with Bladder Urothelial Carcinoma Progression

LINE-1 ORF1 蛋白受活性氧上调并与膀胱尿路上皮癌进展相关

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作者:Patcharawalai Whongsiri, Chaowat Pimratana, Udomsak Wijitsettakul, Depicha Jindatip, Anapat Sanpavat, Wolfgang A Schulz, Michèle J Hoffmann, Wolfgang Goering, Chanchai Boonla

Aim

Reactivation of long interspersed nuclear element-1 (LINE-1) and oxidative stress are suggested to have oncogenic potential to drive tumorigenesis and cancer progression. We previously demonstrated that reactive oxygen species (ROS) caused hypomethylation of LINE-1 elements in bladder cancer cells. In this study, we investigated the expression of LINE-1-encoded protein (ORF1p) and oxidative stress marker 4-hydroxynonenal (4-HNE) in human bladder cancer tissues, as well as induction of ORF1p expression by ROS in bladder cancer cell lines. Materials and

Conclusion

Elevated ORF1p expression is associated with tumor progression. ROS experimentally induce ORF1p expression and promote migration in bladder cancer cells.

Methods

Thirty-six cancerous and 15 non-cancerous adjacent tissues were immunohistochemically stained for ORF1p and 4-HNE. ORF1p expression and cell migration were determined in bladder cancer cells exposed to H2O2

Results

ORF1p and 4-HNE expression was higher in cancerous than non-cancerous tissues. Elevated ORF1p expression was associated with increased 4-HNE expression and with advanced tumors. H2O2 provoked oxidative stress and up-regulated ORF1p expression in VM-CUB-1 compared to the untreated control, and to a lesser degree in TCCSUP. H2O2 exposure enhanced cell migration in UM-UC-3, TCCSUP and VM-CUB-1.

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