胃癌分子标志物环状RNA研究进展

Research progress on circular RNAs as molecular markers for gastric cancer

环状RNA(circular RNA,circRNA)是广泛存在于多物种细胞中结构稳定、高度保守、表达量丰富、可充当微小RNA海绵、具有剪切和转录调控、亲代基因修饰功能的内源性单链闭合circRNA。circRNA主要通过套索驱动的环化、内含子配对驱动的循环、内含子环化方式合成。在胃癌发生和进展过程中,不同种类的circRNA作用不一致。部分circRNA在胃癌组织中表达上调,通过微小RNA/p53/上皮细胞-间充质转化轴等机制促进胃癌细胞增殖、迁移;相反,部分circRNA在胃癌组织中表达下调,通过与miRNA间的海绵作用抑制胃癌细胞增殖和迁移。目前,已在人类唾液、胃液、血浆等成分中检测出胃癌相关的circRNA,提示circRNA具有作为胃癌诊断标志物的潜力。干预circRNA表达提高抗肿瘤药物敏感度,体外合成具有抑癌基因作用的circRNA,或下调具有癌基因作用的circRNA下游信号蛋白是胃癌治疗的有效手段。circRNA为胃癌的诊断和治疗提供了新的思路。

Circular RNA(circRNA)is a type of endogenous single-stranded closed RNA with a stable structure,high conservation,and abundant expression in multiple species.Previous studies have indicated that circRNAs play roles in gene splicing,transcriptional regulation,and parental gene modification by acting as microRNA(miRNA)sponges.circRNAs are primarily synthesized via lariat-driven circularization,intron–pairing–driven circularization,and intron cyclization.The levels of some circRNAs are upregulated in gastric cancer(GC)tissues,and they function as oncogenes to promote the proliferation and migration of GC through the miRNA/p53/epithelial-mesenchymal transition axis and other mechanisms.However,the levels of other circRNAs are down regulated in GC tissues,and they inhibit the proliferation and migration of GC cells by acting as miRNA sponges.Many GC-related circRNAs have been identified in human saliva,gastric juice,and plasma,implying that circRNAs have great potential to be used as biomarkers of GC.Thus,circRNAs may act as a new target in the treatment of GC by intervention of circRNA expression to improve the sensitivity of anti-tumor drugs,synthesis of antioncogenic circRNAs,or down regulation of downstream signaling proteins of oncogenic circRNAs.