School of Medicine, Newgiza University (NGU), Giza, Egypt.
Semin Liver Dis. 2019 Nov;39(4):463-475. doi: 10.1055/s-0039-1688442. Epub 2019 Jun 26.
The role of noncoding transcripts in gene expression is nowadays acknowledged to keep various diseases at bay-despite being referred to as "junk" DNA several years ago. Believed to be at the heart of multiple regulatory pathways, microRNAs (miRNAs) are small noncoding RNAs (ncRNAs) involved in posttranscriptional gene regulation. Recently, the discovery of ncRNAs that compete for shared miRNA pools has dimmed the light on the solo performance of miRNAs in genomic regulation. Indeed, several studies describe RNAs such as long noncoding RNAs, mRNAs, circular RNAs, pseudogenes, and viral RNAs as competing endogenous RNAs (ceRNAs) that sequester miRNAs, allowing for de-repression of downstream miRNA targets. Such integration between coding and noncoding transcripts forms complex ceRNA networks that when dysregulated lead to several diseases such as hepatocellular carcinoma. Here, the authors review perturbed ceRNA networks in hepatocellular carcinoma, describe the role of each in tumorigenesis, and discuss their various clinical implications.
如今,人们已经认识到非编码转录本在基因表达中的作用,可以预防多种疾病——尽管几年前它们还被称为“垃圾”DNA。microRNAs (miRNAs) 是参与转录后基因调控的小非编码 RNA (ncRNAs),被认为是多种调控途径的核心。最近,人们发现 ncRNAs 可以争夺共享的 miRNA 池,这使得 miRNA 在基因组调控中的单独作用变得不那么重要了。事实上,有几项研究将长非编码 RNA、mRNA、环状 RNA、假基因和病毒 RNA 等 RNA 描述为竞争性内源 RNA (ceRNA),它们可以隔离 miRNA,从而允许下游 miRNA 靶基因的去抑制。这种编码和非编码转录物之间的整合形成了复杂的 ceRNA 网络,当这些网络失调时,就会导致多种疾病,如肝细胞癌。在这里,作者综述了肝细胞癌中失调的 ceRNA 网络,描述了它们在肿瘤发生中的作用,并讨论了它们的各种临床意义。