PMID- 29760376 OWN - NLM STAT- MEDLINE DCOM- 20191107 LR - 20191107 IS - 2041-4889 (Electronic) VI - 9 IP - 5 DP - 2018 May 1 TI - The novel 19q13 KRAB zinc-finger tumour suppressor ZNF382 is frequently methylated in oesophageal squamous cell carcinoma and antagonises Wnt/beta-catenin signalling. PG - 573 LID - 10.1038/s41419-018-0604-z [doi] LID - 573 AB - Zinc finger proteins (ZFPs) are the largest transcription factor family in mammals. About one-third of ZFPs are Kruppel-associated box domain (KRAB)-ZFPs and involved in the regulation of cell differentiation/proliferation/apoptosis and neoplastic transformation. We recently identified ZNF382 as a novel KRAB-ZFP epigenetically inactivated in multiple cancers due to frequent promoter CpG methylation. However, its epigenetic alterations, biological functions/mechanism and clinical significance in oesophageal squamous cell carcinoma (ESCC) are still unknown. Here, we demonstrate that ZNF382 expression was suppressed in ESCC due to aberrant promoter methylation, but highly expressed in normal oesophagus tissues. ZNF382 promoter methylation is correlated with ESCC differentiation levels. Restoration of ZNF382 expression in silenced ESCC cells suppressed tumour cell proliferation and metastasis through inducing cell apoptosis. Importantly, ZNF382 suppressed Wnt/beta-catenin signalling and downstream target gene expression, likely through binding directly to FZD1 and DVL2 promoters. In summary, our findings demonstrate that ZNF382 functions as a bona fide tumour suppressor inhibiting ESCC pathogenesis through inhibiting the Wnt/beta-catenin signalling pathway. FAU - Zhang, Chong AU - Zhang C AD - Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. FAU - Xiang, Tingxiu AU - Xiang T AD - Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. FAU - Li, Shuman AU - Li S AD - Department of Oncology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China. FAU - Ye, Lin AU - Ye L AD - Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. FAU - Feng, Yixiao AU - Feng Y AD - Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. FAU - Pei, Lijiao AU - Pei L AD - Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. FAU - Li, Lili AU - Li L AD - Cancer Epigenetics Laboratory, Department of Clinical Oncology, State Key Laboratory of Oncology in South China, Sir YK Pao Center for Cancer and Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong and CUHK-Shenzhen Research Institute, Hong Kong, Hong Kong. FAU - Wang, Xiangyu AU - Wang X AD - Cancer Epigenetics Laboratory, Department of Clinical Oncology, State Key Laboratory of Oncology in South China, Sir YK Pao Center for Cancer and Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong and CUHK-Shenzhen Research Institute, Hong Kong, Hong Kong. FAU - Sun, Ran AU - Sun R AD - Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. FAU - Ren, Guosheng AU - Ren G AD - Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. rgs726@163.com. FAU - Tao, Qian AU - Tao Q AD - Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. qtao@cuhk.edu.hk. AD - Cancer Epigenetics Laboratory, Department of Clinical Oncology, State Key Laboratory of Oncology in South China, Sir YK Pao Center for Cancer and Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong and CUHK-Shenzhen Research Institute, Hong Kong, Hong Kong. qtao@cuhk.edu.hk. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180501 PL - England TA - Cell Death Dis JT - Cell death & disease JID - 101524092 RN - 0 (DNA, Neoplasm) RN - 0 (DNA-Binding Proteins) RN - 0 (Transcription Factors) RN - 0 (Tumor Suppressor Proteins) RN - 0 (ZNF382 protein, human) RN - 0 (beta Catenin) SB - IM MH - Carcinoma, Squamous Cell/genetics/*metabolism/pathology MH - Cell Line, Tumor MH - CpG Islands MH - *DNA Methylation MH - DNA, Neoplasm/genetics/*metabolism MH - DNA-Binding Proteins/*biosynthesis/genetics MH - Esophageal Neoplasms/genetics/*metabolism/pathology MH - *Gene Expression Regulation, Neoplastic MH - Humans MH - *Promoter Regions, Genetic MH - Transcription Factors/*biosynthesis/genetics MH - Tumor Suppressor Proteins/*biosynthesis/genetics MH - *Wnt Signaling Pathway MH - beta Catenin/genetics/metabolism PMC - PMC5951945 COIS- ETHICS APPROVAL AND CONSENT TO PARTICIPATE: All participants provided written consent before enrolment. This study was approved by the Ethics Committees of the First Affiliated Hospital of Chongqing Medical University and conformed to the tenets of the Declaration of Helsinki. CONSENT FOR PUBLICATION: I confirm this manuscript is original. If accepted, the article will not be published elsewhere without the written consent of the publisher. CONFLICT OF INTEREST: The authors declare that they have no conflict of interest. EDAT- 2018/05/16 06:00 MHDA- 2019/11/08 06:00 PMCR- 2018/05/14 CRDT- 2018/05/16 06:00 PHST- 2018/01/16 00:00 [received] PHST- 2018/04/17 00:00 [accepted] PHST- 2018/04/10 00:00 [revised] PHST- 2018/05/16 06:00 [entrez] PHST- 2018/05/16 06:00 [pubmed] PHST- 2019/11/08 06:00 [medline] PHST- 2018/05/14 00:00 [pmc-release] AID - 10.1038/s41419-018-0604-z [pii] AID - 604 [pii] AID - 10.1038/s41419-018-0604-z [doi] PST - epublish SO - Cell Death Dis. 2018 May 1;9(5):573. doi: 10.1038/s41419-018-0604-z.