Epigenetic-Mediated Downregulation of Zinc Finger Protein 671 (ZNF671) Predicts Poor Prognosis in Multiple Solid Tumors.

Jian Zhang,Jieling Zheng,Baiyao Wang,Tao Xie,Jie Lin,Yunhong Tian,Anan Xu,Xiaoting Huang,Ziqi Zheng,Yawei Yuan,Rong Li

doi:10.3389/fonc.2019.00342

Abstract

Zinc finger protein 671 (ZNF671) is a member of the largest transcription factor family in the human genome. However, the methylation status, expression, and prognostic role of ZNF671 in solid tumors remain unclear. The aim of this study was to explore the relationship between ZNF671 and the prognosis of patients with solid tumors. We performed a pan-cancer analysis of the methylation status and mRNA and protein expression of ZNF671 using The Cancer Genome Atlas (TCGA) database and the Human Protein Atlas. We further evaluated the prognostic value of ZNF671 expression among numerous cancer types using the “Kaplan–Meier plotter” (KM plotter) database. We found that downregulation of ZNF671 is associated with hypermethylation of its promoter. Survival analysis established that the downregulation of ZNF671 predicts poor prognosis in breast invasive carcinoma (BRCA), cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), head and neck squamous cell carcinoma (HNSC), kidney renal papillary cell carcinoma (KIRP), lung adenocarcinoma (LUAD), pancreatic adenocarcinoma (PAAD), and uterine corpus endometrial carcinoma (UCEC) solid tumors. CCK-8 and Transwell functional assays showed that ZNF671 could inhibit tumor cell proliferation, migration, and invasion. These results indicate that ZNF671 is an excellent predictive factor for BRCA, CESC, HNSC, KIRP, LUAD, PAAD, SARC, and UCEC solid tumors and may play crucial roles in the development and progression of these tumors.

Highlights

Epigenetic regulation is essential for the normal development and maintenance of gene expression in mammals
Among the 18 cancers examined, the promoter of Zinc finger protein 671 (ZNF671) was hypermethylated in bladder urothelial carcinoma (BLCA), breast invasive carcinoma (BRCA), cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), colon adenocarcinoma (COAD), head and neck squamous cell carcinoma (HNSC), kidney renal clear cell carcinoma (KIRC), kidney renal papillary cell carcinoma (KIRP), liver hepatocellular carcinoma (LIHC), lung adenocarcinoma (LUAD), lung squamous cell carcinoma (LUSC), pancreatic adenocarcinoma (PAAD), prostate adenocarcinoma (PRAD), rectum adenocarcinoma (READ), sarcoma (SARC), skin cutaneous melanoma (SKCM), stomach adenocarcinoma (STAD), and uterine corpus endometrial carcinoma (UCEC) (Figure 1, ∗∗P < 0.01)
To determine the mRNA expression level of ZNF671 in different cancers, we further used the The Cancer Genome Atlas (TCGA) database to validate the mRNA expression of ZNF671 and found that ZNF671 was downregulated in BLCA, BRCA, CESC, COAD, HNSC, KIRP, LUAD, LUSC, PAAD, PRAD, READ, SARC, STAD, thyroid carcinoma (THCA), and UCEC, but the mRNA expression of ZNF671 was upregulated in KIRC, LIHC, and SKCM (Figure 2)

Summary

Introduction

Epigenetic regulation is essential for the normal development and maintenance of gene expression in mammals. Disruption of epigenetic processes can lead to activation of oncogenes and/or the inactivation of tumor suppressor pathways, and the. Tumor Suppressor Gene of ZNF671 accumulation of epigenetic changes in the molecular landscape is a hallmark of cancer [2]. DNA methylation is an early event in tumorigenesis and plays a major role in tumor initiation and progression [3]. It is important to identify reliable prognostic and predictive biomarkers in solid tumors that may help in early diagnosis and treatment strategies. Through recruitment of KRAB-associated protein-1 and other co-repressors, KRABZFPs can regulate cell differentiation, proliferation, apoptosis, tumor suppression, and neoplastic transformation [7,8,9,10,11]. The methylation level and prognostic role of ZNF671 in other tumors are still not clear

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