The novel 19q13 KRAB zinc-finger tumour suppressor ZNF382 is frequently methylated in oesophageal squamous cell carcinoma and antagonises Wnt/β-catenin signalling

Zhang, Chong; Xiang, Tingxiu; Li, Shuman; Ye, Lin; Feng, Yixiao; Pei, Lijiao; Li, Lili; Wang, Xiangyu; Sun, Ryan; Ren, Guosheng; Tao, Qian

doi:10.1038/s41419-018-0604-z

Cited by 27 publications

(27 citation statements)

References 57 publications

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“…In support of this hypothesis, we identified increased H3K27me3 levels at the promoter of many of the H3K27me-depedent migration-repressed genes, such as Rassf7 , Zfp382 , and Tciam ( Figure 5 d–f). Interestingly, Rassf7 was shown to inhibit the MKK7/JNK signaling pathway [ 63 ], Zfp382 was shown to inhibit the transcription of various tumor and migration promoting genes [ 64 , 65 ], and Tciam was found to inhibit LPS signaling and NF-κB activity [ 66 ].…”

Section: Discussionmentioning

confidence: 99%

The Heterochromatin Landscape in Migrating Cells and the Importance of H3K27me3 for Associated Transcriptome Alterations

Segal

Salmon‐Divon

Gerlitz

2018

Cells

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H3K9me3, H3K27me3, and H4K20me1 are epigenetic markers associated with chromatin condensation and transcriptional repression. Previously, we found that migration of melanoma cells is associated with and dependent on global chromatin condensation that includes a global increase in these markers. Taken together with more recent reports by others suggests it is a general signature of migrating cells. Here, to learn about the function of these markers in migrating cells, we mapped them by ChIP-seq analysis. This analysis revealed that induction of migration leads to expansion of these markers along the genome and to an increased overlapping between them. Significantly, induction of migration led to a higher increase in H3K9me3 and H4K20me1 signals at repetitive elements than at protein-coding genes, while an opposite pattern was found for H3K27me3. Transcriptome analysis revealed 182 altered genes following induction of migration, of which 33% are dependent on H3K27me3 for these changes. H3K27me3 was also required to prevent changes in the expression of 501 other genes upon induction of migration. Taken together, our results suggest that heterochromatinization in migrating cells is global and not restricted to specific genomic loci and that H3K27me3 is a key component in executing a migration-specific transcriptional plan.

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Section: Discussionmentioning

confidence: 99%

The Heterochromatin Landscape in Migrating Cells and the Importance of H3K27me3 for Associated Transcriptome Alterations

Segal

Salmon‐Divon

Gerlitz

2018

Cells

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“…We thus investigated the functions of ZNF471 in breast cancer. Previous studies have shown that KRAB-ZFPs are associated with cancer cell proliferation and are important for other biological functions, including apoptosis and migration/invasion in several tumors [ 21 , 23 , 33 ]. Therefore, the tumor-suppressive functions of ZNF471 in breast cancer were first investigated in this study.…”

Section: Discussionmentioning

confidence: 99%

The tumor suppressor Zinc finger protein 471 suppresses breast cancer growth and metastasis through inhibiting AKT and Wnt/β-catenin signaling

et al. 2020

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Background Zinc-finger protein 471 (ZNF471) is a member of the Krüppel-associated box domain zinc finger protein (KRAB-ZFP) family. ZNF471 is methylated in squamous cell carcinomas of tongue, stomach and esophageal. However, its role in breast carcinogenesis remains elusive. Here, we studied its expression, functions, and molecular mechanisms in breast cancer. Methods We examined ZNF471 expression by RT-PCR and qPCR. Methylation-specific PCR determined its promoter methylation. Its biological functions and related molecular mechanisms were assessed by CCK-8, clonogenicity, wound healing, Transwell, nude mice tumorigenicity, flow cytometry, BrdU-ELISA, immunohistochemistry and Western blot assays. Results ZNF471 was significantly downregulated in breast cell lines and tissues due to its promoter CpG methylation, compared with normal mammary epithelial cells and paired surgical-margin tissues. Ectopic expression of ZNF471 substantially inhibited breast tumor cell growth in vitro and in vivo, arrested cell cycle at S phase, and promoted cell apoptosis, as well as suppressed metastasis. Further knockdown of ZNF471 verified its tumor-suppressive effects. We also found that ZNF471 exerted its tumor-suppressive functions through suppressing epithelial-mesenchymal transition, tumor cell stemness and AKT and Wnt/β-catenin signaling. Conclusions ZNF471 functions as a tumor suppressor that was epigenetically inactivated in breast cancer. Its inhibition of AKT and Wnt/β-catenin signaling pathways is one of the mechanisms underlying its anti-cancer effects.

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“…ZNF382 also inhibited the proliferation and metastasis of ESCC cells by inhibiting the Wnt/beta-catenin signaling pathway. These data suggest that ZNF382 plays a role in inhibiting the formation of ESCCs [ 18 ]. ZNF382 is also methylated in a range of primary tumors (nasopharyngeal, esophageal, colon, stomach, and breast).…”

Section: Discussionmentioning

confidence: 99%

A Three Protein-Coding Gene Prognostic Model Predicts Overall Survival in Bladder Cancer Patients

Ning

Wang

et al. 2020

BioMed Research International

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Bladder cancer (BLCA) is the most common urinary tract tumor and is the 11th most malignant cancer worldwide. With the development of in-depth multisystem sequencing, an increasing number of prognostic molecular markers have been identified. In this study, we focused on the role of protein-coding gene methylation in the prognosis of BLCA. We downloaded BLCA clinical and methylation data from The Cancer Genome Atlas (TCGA) database and used this information to identify differentially methylated genes and construct a survival model using lasso regression. We assessed 365 cases, with complete information regarding survival status, survival time longer than 30 days, age, gender, and tumor characteristics (grade, stage, T, M, N), in our study. We identified 353 differentially methylated genes, including 50 hypomethylated genes and 303 hypermethylated genes. After annotation, a total of 227 genes were differentially expressed. Of these, 165 were protein-coding genes. Three genes (zinc finger protein 382 (ZNF382), galanin receptor 1 (GALR1), and structural maintenance of chromosomes flexible hinge domain containing 1 (SMCHD1)) were selected for the final risk model. Patients with higher-risk scores represent poorer survival than patients with lower-risk scores in the training set ( HR = 2.37 , 95% CI 1.43-3.94, p = 0.001 ), in the testing group ( HR = 1.85 , 95% CI 1.16-2.94, p = 0.01 ), and in the total cohort ( HR = 2.06 , 95% CI 1.46-2.90, p < 0.001 ). Further univariate and multivariate analyses using the Cox regression method were conducted in these three groups, respectively. All the results indicated that risk score was an independent risk factor for BLCA. Our study screened the different methylation protein-coding genes in the BLCA tissues and constructed a robust risk model for predicting the outcome of BLCA patients. Moreover, these three genes may function in the mechanism of development and progression of BLCA, which should be fully clarified in the future.

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The novel 19q13 KRAB zinc-finger tumour suppressor ZNF382 is frequently methylated in oesophageal squamous cell carcinoma and antagonises Wnt/β-catenin signalling

Cited by 27 publications

References 57 publications

The Heterochromatin Landscape in Migrating Cells and the Importance of H3K27me3 for Associated Transcriptome Alterations

The Heterochromatin Landscape in Migrating Cells and the Importance of H3K27me3 for Associated Transcriptome Alterations

The tumor suppressor Zinc finger protein 471 suppresses breast cancer growth and metastasis through inhibiting AKT and Wnt/β-catenin signaling

A Three Protein-Coding Gene Prognostic Model Predicts Overall Survival in Bladder Cancer Patients

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