KRAB zinc finger protein ZNF382 is a proapoptotic tumor suppressor that represses multiple oncogenes and is commonly silenced in multiple carcinomas.

Zinc finger transcription factors are involved broadly in development and tumorigenesis. Here, we report that the little studied zinc finger transcription factor ZNF382 functions as a tumor suppressor in multiple carcinomas. Although broadly expressed in normal tissues, ZNF382 expression was attenuated in multiple carcinoma cell lines due to promoter CpG methylation. ZNF382 was also frequently methylated in multiple primary tumors (nasopharyngeal, esophageal, colon, gastric, and breast). Ectopic expression of ZNF382 in silenced tumor cells significantly inhibited their clonogenicity and proliferation and induced apoptosis. We further found that ZNF382 inhibited NF-kappaB and AP-1 signaling and downregulated the expression of multiple oncogenes including MYC, MITF, HMGA2, and CDK6, as well as the NF-kappaB upstream factors STAT3, STAT5B, ID1, and IKBKE, most likely through heterochromatin silencing. ZNF382 could suppress tumorigenesis through heterochromatin-mediated silencing, as ZNF382 was colocalized and interacted with heterochromatin protein HP1 and further changed the chromatin modifications of ZNF382 target oncogenes. Our data show that ZNF382 is a functional tumor suppressor frequently methylated in multiple carcinomas.

Cheng Y ，Geng H ，Cheng SH ，Liang P ，Bai Y ，Li J ，Srivastava G ，Ng MH ，Fukagawa T ，Wu X ，Chan AT ，Tao Q ... -  《-》

KRAB zinc-finger protein 382 regulates epithelial-mesenchymal transition and functions as a tumor suppressor, but is silenced by CpG methylation in gastric cancer.

Pei L ，He X ，Li S ，Sun R ，Xiang Q ，Ren G ，Xiang T ... -  《-》

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

Zhang C ，Xiang T ，Li S ，Ye L ，Feng Y ，Pei L ，Li L ，Wang X ，Sun R ，Ren G ，Tao Q ... -  《Cell Death & Disease》

A novel 19q13 nucleolar zinc finger protein suppresses tumor cell growth through inhibiting ribosome biogenesis and inducing apoptosis but is frequently silenced in multiple carcinomas.

Epigenetic disruption of tumor suppressor genes is frequently involved in tumorigenesis. We identified a novel 19q13 KRAB domain-containing zinc finger protein, ZNF545/ZFP82, broadly expressed in normal tissues but downregulated in multiple tumor cell lines. The ZNF545 promoter contains a CpG island, which is frequently methylated in cell lines. The transcriptional silencing of ZNF545 could be reversed by pharmacologic or genetic demethylation, indicating direct epigenetic silencing. ZNF545 was also frequently methylated in multiple primary tumors of nasopharyngeal, esophageal, lung, gastric, colon, and breast, but rarely in normal epithelial tissues and paired normal tissues. ZNF545 is located in the nucleus and mainly sequestered in nucleoli, functioning as a repressor. ZNF545 is able to repress NF-κB and AP-1 signaling pathways, whereas ectopic expression of ZNF545 in silenced tumor cells significantly inhibited their growth and induced apoptosis. Functional studies showed that ZNF545 was involved in ribosome biogenesis through inhibiting the activity of rDNA promoter and decreasing cellular protein translation efficiency. Thus, we identified ZNF545 as a novel tumor suppressor inducing tumor cell apoptosis, repressing ribosome biogenesis and target gene transcription. The tumor-specific methylation of ZNF545 could be an epigenetic biomarker for cancer diagnosis.

Cheng Y ，Liang P ，Geng H ，Wang Z ，Li L ，Cheng SH ，Ying J ，Su X ，Ng KM ，Ng MH ，Mok TS ，Chan AT ，Tao Q ... -  《-》

ZNF382: A transcription inhibitor down-regulated in multiple tumors due to promoter methylation.

Zinc finger protein 382 (ZNF382), a member of the Krüppel-associated box zinc finger proteins (KRAB-ZFPs) family, plays critical roles in regulating certain downstream genes expression as a transcription inhibitor. ZNF382 is downregulated in multiple tumors due to hypermethylation of its promoter, to be more specific, methylation of promoter CpG island may contributes to inhibition of gene expression as found in many studies. With application of DNA methyltransferase inhibitors (DNMTi) 5-azacytidine and 5-aza-2'-deoxycytidine, hypomethylation of ZNF382 gene may contribute to anti-tumor effects. This review summerized the structure, biological functions, expression and the roles of ZNF382 in multiple cancers, and, expression of ZNF382 regulated by promoter methylation was further discussed to show the possibilities of DNA hypomethylation treatment as a potential treatment in clinical applications.

Chen S ，Xiao Z ，Zhou J ，Yang M ，Feng S ，Huang Q ，Zou J ，Zeng T ，Li Y ，Peng L ，Zeng Y ，Zeng X ... -  《-》