可变剪接在卵巢癌中的作用研究进展

Research Progress on the Role of Variable Splicing in Ovarian Cancer

卵巢癌(ovarian cancer, OC)是发生在卵巢的恶性肿瘤性疾病。卵巢癌大多发病隐匿,进展迅速,加之缺乏高效的早期诊断措施,许多病人初次诊断时已属晚期。在诊断和治疗方面已取得了一定的进展,但其五年生存率仍然低,所以迫切需要研究OC的发生和发展机制。中心法则中RNA是由DNA转录而来的,作为一个转录本来源的DNA转录区域却不一定是由某个连续DNA片段提供的,甚至可能有间隔DNA转录区的交叉,不同区域不同顺序的转录产物共同组成一个转录本,极大增加了DNA产生RNA的复杂度。人类基因组中多数基因都会发生RNA的可变剪接(alternative splicing, AS),AS可实现相同的前信使RNA生成多个mRNA剪接异构体和下游蛋白质亚型。一个基因的不同编码区可以以不同的方式剪接,导致该基因的多种转录状态,最终的蛋白产物可能具有不同的或相互拮抗的功能和结构特征。这在很大程度上扩大了人类基因的复杂性和多样性,影响着肿瘤细胞表型和信号通路,从而影响肿瘤的发生、发展。OC中也发现可变剪接事件,笔者就AS在OC中的作用作综述。

Ovarian cancer (OC) is a malignant tumor disease that occurs in the ovaries. The incidence of ovari-an cancer is mostly hidden, rapid progress, coupled with the lack of efficient early diagnosis measures, many patients are in the late stage when they are diagnosed for the first time. Some pro-gress has been made in diagnosis and treatment, but the five-year survival rate is still low. There-fore, there is an urgent need to study the occurrence and development mechanism of OC. In the central rule, RNA is transcribed from DNA, but the DNA transcriptional region as a transcript source is not necessarily provided by a continuous DNA fragment, and there may even be intersecting DNA transcripts. Transcripts from different regions and different sequences form a transcript, which greatly increases the complexity of DNA to produce RNA. However, RNA alternative splicing (alter-native splicing, AS) occurs in most genes in the human genome, and AS can achieve the same pre-messenger that enables RNA to produce multiple mRNA splicing isomers and downstream protein subtypes. Different coding regions of a gene can be spliced in different ways, resulting in a variety of transcriptional states of the gene, and the final protein products may have different or mutually antagonistic functional and structural characteristics. This greatly expands the complexity and diversity of human genes and affects the phenotype and signal pathway of tumor cells, thus af-fecting the occurrence and development of tumors. Alternative splicing events are also found in OC. The author summarizes the role of AS in OC.