Gene expression and DNA methylation regulation of arsenic in mouse bladder tissues and in human urothelial cells

Jou,Yeong‑Chin; Wang,Shou‑Chieh; Dai,Yuan‑Chang; Chen,Shih‑Ying; Shen,Cheng‑Huang; Lee,Ying‑Ray; Chen,Lei‑Chin; Liu,Yi‑Wen

doi:10.3892/or.2019.7235

Gene expression and DNA methylation regulation of arsenic in mouse bladder tissues and in human urothelial cells

Authors:
- Yeong‑Chin Jou
- Shou‑Chieh Wang
- Yuan‑Chang Dai
- Shih‑Ying Chen
- Cheng‑Huang Shen
- Ying‑Ray Lee
- Lei‑Chin Chen
- Yi‑Wen Liu
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Affiliations: Department of Urology, Ditmanson Medical Foundation Chiayi Christian Hospital, Chiayi 600, Taiwan, R.O.C., Division of Nephrology, Department of Internal Medicine, Kuang Tien General Hospital, Taichung 437, Taiwan, R.O.C., Department of Microbiology, Immunology and Biopharmaceuticals, College of Life Sciences, National Chiayi University, Chiayi 600, Taiwan, R.O.C., Department of Medical Research, Ditmanson Medical Foundation Chiayi Christian Hospital, Chiayi 600, Taiwan, R.O.C., Department of Nutrition, I‑Shou University, Jiaosu, Yanchao, Kaohsiung 82445, Taiwan, R.O.C.
Published online on: July 16, 2019 https://doi.org/10.3892/or.2019.7235
Pages: 1005-1016
Copyright: © Jou et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

According to a report of the International Agency for Research on Cancer, arsenic and inorganic arsenic compounds are classified into Group 1 carcinogens with regard to human health. Epidemiological studies indicate that arsenic is one of the main risk factors for the development of bladder cancer. In the present study, arsenic‑altered gene expression in mouse bladder tissues and in human urothelial cells was compared. In the mouse model, sodium arsenite‑induced mouse urothelial hyperplasia and intracellular inclusions were present. Following DNA array analysis, four genes with differential expression were selected for quantitative real‑time PCR assay. The genes were the following: Cystathionine β‑synthase (CBS), adenosine A1 receptor (ADORA1), metastasis‑associated lung adenocarcinoma transcript 1 (MALAT1) and Wnt inhibitory factor 1 (Wif1). The results indicated a significant increase in the levels of Cbs and Adora1. The analysis of the DNA CpG methylation levels of the mouse Cbs and Adora1 genes revealed no significant change. In contrast to these observations, the four genes were further analyzed in the human normal urothelial cell line SV‑HUC1. The data indicated that WIF1 gene expression was decreased by sodium arsenite, whereas this was not noted for CBS, MALAT1 and ADORA1. Sodium arsenite decreased mRNA and protein expression levels of the WIF1 gene. In addition, the methylation levels of the WIF1 gene were increased. Sodium arsenite inhibited cell proliferation and promoted cell migration as demonstrated in cell functional assays. The gene status was compared in 8 human urothelial cell lines, and WIF1 mRNA expression levels were determined to be higher, whereas DNA CpG methylation levels were lower in SV‑HUC1 cells compared with those noted in the other 7 bladder cancer cell lines. In summary, the data indicated that sodium arsenite decreased WIF1 gene expression and promoted cell migration. The increased methylation levels of WIF1 DNA CpG could be a potential biomarker for bladder cancer.

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