长链非编码RNA作为竞争性内源RNA及其靶向技术在胰腺癌中的研究进展

Research progress of long non-coding RNA as competitive endogenous RNA and its targeting technology in pancreatic cancer

目的总结长链非编码RNA(long non-coding RNA,lncRNA)作为竞争性内源RNA(competitive endogenous RNA,ceRNA)及其靶向技术在胰腺癌中的最新研究,为lncRNA靶向干预或作为胰腺癌早期诊断标志物提供新思路。方法检索国内外有关lncRNA作为ceRNA及其靶向技术在胰腺癌中的相关研究的文献并予以综述。结果目前越来越多的证据表明,在肿瘤等病理状态下,细胞内lncRNA的丰度可引发ceRNA串扰,lncRNA通过miRNA应答元件与miRNA不完全碱基互补结合发挥类似于“海绵”的作用而吸附miRNA,从而改变miRNA的活性和有效性,同时调节下游靶基因的表达。目前已有大量研究鉴定了lncRNA介导的ceRNA调控网络即lncRNA/miRNA/mRNA轴,通过多种细胞功能在胰腺癌的发生和进展中发挥促癌或抑癌作用。此外,较多靶向lncRNA的技术如小干扰RNA、反义寡核苷酸、成簇规律间隔的短回文重复序列(clustered regularly interspaced short palindromic repeats,CRISPR)/CRISPR相关蛋白9、小分子抑制剂等已广泛开展了临床前研究并取得重要成果。结论ceRNA假说中非编码RNA与具有非编码特性的mRNA组成的功能复合体,在转录组上形成一个多水平、跨调控的ceRNA网络。通过ceRNA网络机制实现lncRNA表观遗传修饰和关键的转录后调控,已成为一种探讨lncRNA功能的成功范式,已有较多研究探索了诸多lncRNA在胰腺癌发生和发展中的抑癌和促癌作用及其机制研究,并且靶向lncRNA技术的不断进步为研究lncRNA提供了条件,lncRNA有潜力作为胰腺癌癌前诊断和预后的生物标志物。

Objective To summarize the latest research of long non-coding RNA(lncRNA)as competitive endogenous RNA(ceRNA)and its targeting technology in pancreatic cancer,so as to provide new ideas for lncRNA targeted intervention or as an early diagnostic marker of pancreatic cancer.Method The domestic and foreign literature on researches of lncRNA as ceRNA and its targeting technology in the pancreatic cancer was searched and reviewed.Results At present,the growing number of evidences showed that in pathological states such as tumors,the abundance of intracellular lncRNAs was sufficient to trigger ceRNA crosstalk.The lncRNA played a role like“sponge”through the complementary binding of incomplete base of miRNA with miRNA response elements,then adsorbed miRNA,and thus changed the activity and effectiveness of miRNA.It also regulated the expression of downstream target genes.Moreover,a large number of studies had identified that the lncRNA-mediated ceRNA regulatory network,namely lncRNA/miRNA/mRNA axis,played a role in promoting or inhibiting the occurrence and progression of pancreatic cancer through a variety of cellular functions.In addition,many technologies targeting lncRNA,such as small interfering RNA,antisense oligonucleotides,clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated protein 9,and small molecule inhibitors,etc.had been widely studied and acquired important results in preclinical research.Conclusions The ceRNA hypothesis is a functional complex composed by non-coding RNAs and mRNAs with non-coding properties,forming a ceRNA network of multi-level and cross-regulatory on the transcriptome.Epigenetic modification and key post-transcriptional regulation of lncRNA have been achieved through ceRNA network mechanism,which has become a successful paradigm for exploring the function of lncRNA.The tumor suppressive and promoting effects and mechanisms of many lncRNAs in the occurrence and development of pancreatic cancer are explored in many studies.Moreover,the continuous progress of targeted lncRNA technology provides conditions for study of lncRNA.LncRNA has a potential to be used as a biomarker for precancerous diagnosis and prognosis of pancreatic cancer.