Abstract
ZNF750 controls epithelial homeostasis by regulating epidermal-differentiation genes, a role underscored by its pathogenic mutations in esophageal squamous cell cancers (SCCs). However, the precise role of ZNF750 in SCC cell biology remains unclear. In this study, we report that ZNF750 is exclusively deleted, mutated and underexpressed in human SCCs, and low ZNF750 expression is associated with poor survival. Restoration of wildtype, but not mutant ZNF750 protein uniquely inhibited the malignant phenotypes of SCC cells both in vitro and in vivo. Notably, ZNF750 promoted the expression of a long non-coding RNA (TINCR), which mediated both cancer-inhibition and differentiation-induction effects of ZNF750. In addition, ZNF750 potently suppressed cell migration by directly inhibiting the transactivation of LAMC2. Together, our findings characterize ZNF750 as a crucial SCC-specific suppressor and uncover its novel anticancer-associated functions.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Carcinoma, Squamous Cell / genetics*
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Carcinoma, Squamous Cell / physiopathology
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Cell Differentiation / genetics
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Cell Line, Tumor
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Cell Lineage
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Cell Movement
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DNA, Neoplasm
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Esophageal Neoplasms / genetics*
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Esophageal Neoplasms / physiopathology
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Female
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Gene Deletion
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Gene Expression Regulation, Neoplastic
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Genes, Tumor Suppressor*
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HEK293 Cells
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Head and Neck Neoplasms / genetics
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Humans
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Laminin / genetics
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Mice
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Mice, Inbred NOD
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Mutation
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Oligonucleotide Array Sequence Analysis
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Prognosis
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RNA, Long Noncoding
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Transcription Factors / genetics*
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Transcription Factors / metabolism
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Transcriptome
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Tumor Suppressor Proteins / metabolism
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Uterine Cervical Neoplasms / genetics
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Uterine Cervical Neoplasms / physiopathology
Substances
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DNA, Neoplasm
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LAMC2 protein, human
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Laminin
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RNA, Long Noncoding
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TP63 protein, human
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Transcription Factors
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Tumor Suppressor Proteins
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ZNF750 protein, human