c‑Jun suppresses the expression of WNT inhibitory factor 1 through transcriptional regulation and interaction with DNA methyltransferase 1 in gallbladder cancer

Lin,Bin; Hong,Haijie; Jiang,Xiaojie; Li,Chengzong; Zhu,Siyuan; Tang,Nanhong; Wang,Xiaoqian; She,Feifei; Chen,Yanling

doi:10.3892/mmr.2018.8890

c‑Jun suppresses the expression of WNT inhibitory factor 1 through transcriptional regulation and interaction with DNA methyltransferase 1 in gallbladder cancer

Authors:
- Bin Lin
- Haijie Hong
- Xiaojie Jiang
- Chengzong Li
- Siyuan Zhu
- Nanhong Tang
- Xiaoqian Wang
- Feifei She
- Yanling Chen
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Affiliations: Department of Hepatobiliary Surgery and Fujian Institute of Hepatobiliary Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, P.R. China, Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fuzhou, Fujian 350108, P.R. China
Published online on: April 16, 2018 https://doi.org/10.3892/mmr.2018.8890
Pages: 8180-8188
Copyright: © Lin et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

WNT inhibitory factor 1 (WIF‑1) is involved in the tumorigenicity and progression of several types of tumor, which has been attributed to aberrant hypermethylation of its promoter. However, the role of WIF‑1 in the pathogenesis of gallbladder cancer (GBC) remains to be fully elucidated, and the data available are insufficient to identify the upstream molecular mechanisms involved. In the present study, the methylation status of the WIF‑1 promoter was investigated using methylation‑specific polymerase chain reaction (PCR) and bisulfate sequencing PCR in GBC cells. Immunohistochemistry, reverse transcription‑quantitative PCR and western blotting were used to analyze the expression of WIF‑1 and c‑Jun. In addition, a co‑immunoprecipitation assay was designed to determine the DNA methyltransferase that was implicated in WIF‑1 methylation. The results revealed that the expression of WIF‑1 was low in GBC, and that this was caused by aberrant DNA hypermethylation. However, there were no significant correlations between the expression of WIF‑1 and certain key clinicopathological characteristics of GCB. Subsequently, a negative correlation was found between the protein expression of c‑Jun and WIF‑1 in 50 GBC specimens using immunohistochemistry. The demethylation and re‑expression of WIF‑1 was observed when the expression of c‑Jun was silenced. Finally, it was found that the knockdown of c‑Jun downregulated the expression of DNA methyltransferase 1 (DNMT1) and that c‑Jun interacted with DNMT1. Taken together, the present study suggested that c‑Jun suppressed the expression of WIF‑1 through transcriptional regulation and interaction with DNMT1 in GBC. These findings provide an alternative pathogenesis of GBC, which may be promising as a novel reference for early diagnosis or future treatment.

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