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cAMP反应元件结合蛋白(cAMP responsive element binding protein,CREB)是亮氨酸拉链家族转录因子。新近研究发现,其在肿瘤组织中的表达显著高于癌旁,被认为是体内的原癌基因之一。非编码RNA(non-coding RNA,ncRNA)是生物体内不能翻译成蛋白质的RNA,主要包括微小RNA(microRNA,miRNA)和长链非编码RNA(long non-coding RNA,lncRNA)等,其异常表达与肿瘤的发生发展密切相关,是目前肿瘤研究的热点。研究表明,CREB与ncRNA之间存在互动效应,并且二者之间的相互作用影响肿瘤的发生发展,然而miRNA和lncRNA的作用机制却不相同。肿瘤细胞内高表达的CREB在影响下游靶基因表达时能够正调控miRNA,而对lncRNA则有促进和抑制两方面的作用。反之,肿瘤细胞中一些低表达的miRNA能促进CREB的表达;有趣的是,高表达的lncRNA能够促进CREB的表达和诱导其活性增强。在影响下游靶基因表达时miRNA仅仅发挥抑制作用,而lncRNA则分别具有促进和抑制作用。本文结合我们的系列报道和最新的研究结果,对ncRNA与CREB的互动效应及其与肿瘤的发生发展之间的关系作一综述。
The cAMP responsive element binding protein (CREB) is a leucine zipper family transcription factor. Recent studies have found that its expression in tumor tissues was significantly higher than the adjacent cancer, is considered to be one of the proto-oncogene in vivo. Non-coding RNA (ncRNA) is an RNA that can not be translated into a protein in an organism and mainly includes microRNA (miRNA) and long non-coding RNA (lncRNA), which are abnormally expressed It is closely related to the occurrence and development of tumors and is the hot point of cancer research at present. Studies have shown that there is interaction between CREB and ncRNA, and the interaction between them affects tumor development, however, the mechanism of miRNA and lncRNA are not the same. The high expression of CREB in tumor cells can positively regulate miRNA while affecting the expression of downstream target genes, and promote and inhibit lncRNA in both aspects. Conversely, some low-expressed miRNAs in tumor cells can promote the expression of CREB. Interestingly, highly expressed lncRNA can promote CREB expression and induce its activity. While affecting the expression of downstream target genes, miRNAs exert their inhibitory effects only, whereas lncRNAs promote and inhibit, respectively. Based on our series of reports and the latest research results, this article reviews the interaction between ncRNA and CREB and its relationship with the development of tumors.