Idogawa Masashi, Ohashi Tomoko, Sasaki Yasushi, Nakase Hiroshi, Tokino Takashi
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.
Int J Cancer. 2017 Jun 15;140(12):2785-2791. doi: 10.1002/ijc.30689. Epub 2017 Mar 27.
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.
p53是最重要的肿瘤抑制基因之一，必须探索p53的直接转录靶点以阐明其功能机制。迄今为止，主要研究的p53靶点是蛋白质编码基因。我们之前的研究表明，几种长链非编码RNA（lncRNA）是p53的直接转录靶点，敲低特定的lncRNA可调节p53诱导的细胞凋亡。在本研究中，对p53的下一代染色质免疫沉淀测序（ChIP-seq）数据的分析表明，lncRNA NEAT1是p53的直接转录靶点。p53对NEAT1诱导的抑制减弱了p53对癌细胞生长的抑制作用，还调节基因反式激活，包括许多lncRNA的反式激活。此外，NEAT1的低表达与几种癌症的不良预后相关。这些结果表明，NEAT1表达的诱导有助于p53的肿瘤抑制功能，并提示p53和NEAT1构成一个转录网络，有助于各种生物学功能和肿瘤抑制。
