CREB与其相关的非编码RNA在肿瘤发生发展中的作用

Effects of CREB and Its Related Non-coding RNA in Tumorigenesis

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。

cAMP responsive element binding protein（CREB） is a transcription factor of the leucine zipper family.Recent studies found that CREB,which was overexpressed in tumor tissues and cells compared with control,was confirmed to be an important proto-oncogene in many cancers.Non-coding RNAs（ncRNAs） which mainly include microRNAs（miRNAs） and long non-coding RNAs（lncRNAs）,are non-protein coding transcripts involved in tumorigenesis.Recent reports showed that CREB interacted with ncRNAs and contributed to tumorigenesis.However,different mechanisms were involved when compared miRNAs with lncRNAs.Overexpressed CREB in tumor cells could positively regulate miRNAs,whereas both positive and negative effects were observed in the CREB-regulated expression of lncRNAs.Furthermore,miRNAs played an inhibitory role in the expression of its target genes,whereas lncRNAs elicited both inhibitory and excitatory effects.Based on recent publications,we reviewed the interaction effects between CREB and ncRNA,and their roles in tumor development and progression.