title: Long non-coding RNA NEAT1 is a transcriptional target of p53 and modulates p53-induced transactivation and tumor-suppressor function.
abstract: p53 is one of the most important tumor suppressor genes, and the direct transcriptional targets of p53 must be explored to elucidate its functional mechanisms. Thus far, the p53 targets that have been primarily studied are protein-coding genes. Our previous study revealed that several long non-coding RNAs (lncRNAs) are direct transcriptional targets of p53, and knockdown of specific lncRNAs modulates p53-induced apoptosis. In this study, analysis of next-generation chromatin immunoprecipitation-sequencing (ChIP-seq) data for p53 revealed that the lncRNA NEAT1 is a direct transcriptional target of p53. The suppression of NEAT1 induction by p53 attenuates the inhibitory effect of p53 on cancer cell growth and also modulates gene transactivation, including that of many lncRNAs. Furthermore, low expression of NEAT1 is related to poor prognosis in several cancers. These results indicate that the induction of NEAT1 expression contributes to the tumor-suppressor function of p53 and suggest that p53 and NEAT1 constitute a transcriptional network contributing to various biological functions and tumor suppression.
authors.affiliation: Department of Medical Genome Sciences, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.|Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Idogawa
authors.affiliation: Department of Medical Genome Sciences, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.|Japan Society for the Promotion of Science (JSPS), Tokyo, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Ohashi
authors.affiliation: Department of Medical Genome Sciences, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.|Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Sasaki
authors.affiliation: Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakase
authors.affiliation: Department of Medical Genome Sciences, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Takashi
authors.identifier: 0000-0001-9428-9543
authors.initials: T
authors.lastname: Tokino
mesh_terms: D000072283:A549 Cells; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D006801:Humans; D053208:Kaplan-Meier Estimate; D061986:MCF-7 Cells; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D034622:RNA Interference; D062085:RNA, Long Noncoding / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015533:Transcriptional Activation; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: C577276:NEAT1 long non-coding RNA, human; D062085:RNA, Long Noncoding; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins
keywords: NEAT1; lncRNA; p53; transcriptional regulation