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Mechanism for the malignant phenotype of nasopharyngeal carcinoma (NPC) remains poorly understood. Epstein-Barr virus (EBV) consistently appears in nearly all malignant NPC patient samples, suggesting the strong etiological link between the malignant phenotype and EBV infection. Here we found that the EBV-encoded latent membrane protein (LMP1) enhanced cell growth, motility, invasion and xenograft tumor growth of NPC. RNA-seq profiling analysis of LMP1-positive NPC patient tissues indicated that widespread gene repression contributed to malignant phenotype of NPC. The transcription factor binding site (TFBS) enrichment analysis indicated a subset of transcription factors including ATOH8, a novel transcript factor which belongs to the basic helix-loop-helix (bHLH) gene family inversely enriched in promoters of up-regulated genes and down-regulated genes. Importantly, the expression of ATOH8 was suppressed in both immortalized normal nasopharyngeal epithelial cells (NPEC) and NPC cells with LMP1 overexpression. The Real-Time PCR and Western Blot assays indicated that ATOH8 decreased expression in NPC cell lines and patient samples. Moreover, by gain- or loss-of-function assays, we demonstrated that ATOH8 inhibition promoted malignant phenotype, whereas ATOH8 restoration reversed malignant phenotype of NPC. Finally, we demonstrated that LMP1 inhibited ATOH8 expression by epigenetically impairing the occupancy of activating H3K4me3 and enhancing the occupancy of repressive H3K27me3 on ATOH8 promoter. Collectively, our study uncovered the occurrence of malignant phenotype of NPC induced by EBV infection and characterized a novel bHLH transcription factor ATOH8 as a new downstream target of LMP1.
Pubmed ID: 27049918
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Non-profit plasmid repository dedicated to helping scientists around the world share high-quality plasmids. Facilitates archiving and distributing DNA-based research reagents and associated data to scientists worldwide. Repository contains over 65,000 plasmids, including special collections on CRISPR, fluorescent proteins, and ready-to-use viral preparations. There is no cost for scientists to deposit plasmids, which saves time and money associated with shipping plasmids themselves. All plasmids are fully sequenced for validation and sequencing data is openly available. We handle the appropriate Material Transfer Agreements (MTA) with institutions, facilitating open exchange and offering intellectual property and liability protection for depositing scientists. Furthermore, we curate free educational resources for the scientific community including a blog, eBooks, video protocols, and detailed molecular biology resources.
View all literature mentionsOpen source database of curated, non-redundant set of profiles derived from published collections of experimentally defined transcription factor binding sites for multicellular eukaryotes. Consists of open data access, non-redundancy and quality. JASPAR CORE is smaller set that is non-redundant and curated. Collection of transcription factor DNA-binding preferences, modeled as matrices. These can be converted into Position Weight Matrices (PWMs or PSSMs), used for scanning genomic sequences. Web interface for browsing, searching and subset selection, online sequence analysis utility and suite of programming tools for genome-wide and comparative genomic analysis of regulatory regions. New functions include clustering of matrix models by similarity, generation of random matrices by sampling from selected sets of existing models and a language-independent Web Service applications programming interface for matrix retrieval.
View all literature mentionsEncyclopedia of DNA elements consisting of list of functional elements in human genome, including elements that act at protein and RNA levels, and regulatory elements that control cells and circumstances in which gene is active. Enables scientific and medical communities to interpret role of human genome in biology and disease. Provides identification of common cell types to facilitate integrative analysis and new experimental technologies based on high-throughput sequencing. Genome Browser containing ENCODE and Epigenomics Roadmap data. Data are available for entire human genome.
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View all literature mentionsCell line CNE-1 is a Hybrid cell line with a species of origin Homo sapiens (Human)
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