竞争内源性RNA在骨肉瘤发生发展中的作用研究进展

Research progress of competing endogenous RNA in osteosarcoma

骨肉瘤是最常见的儿童和青少年原发恶性骨肿瘤,具有恶性程度高、进展迅速、转移潜能高的特点。近几十年来,骨肉瘤的治疗并没有取得明显的进展,其主要原因是对骨肉瘤的发病机制缺乏系统和深入的认识。越来越多的证据表明,不同种类RNA在骨肉瘤的发生发展中起着关键的调控作用。竞争内源性RNA(competing endogenous RNA,ceRNA)是近年来兴起的学说,是指信使RNA(messenger RNA,mRNA)、长链非编码RNA(long non-coding RNA,lncRNA)、假基因等不同转录物之间通过竞争结合微小RNA(microRNA,miRNA)发挥相互调控作用。这些转录物之间的相互调控在骨肉瘤发生发展中起着重要作用,包括介导骨肿瘤细胞增殖、凋亡、转移、化疗耐药等生物学过程。此外,这些不同种类的转录物还可能为骨肉瘤提供新的生物标志物和潜在的有效治疗靶点。通过回顾ceRNA假说的发展历程,并对ceRNA的现有知识体系进行归纳,阐述了不同类型ceRNA在骨肉瘤发生发展机制中的相互作用及其涉及的生物学功能,以期为骨肉瘤的基础及临床研究奠定基础,促进骨肉瘤的早期诊断和治疗预后。

Osteosarcoma,the most common primary bone tumor in children and adolescents,is characterized by high malignancy,rapid progression and high metastatic potential.However,no significant progress has been made in treating osteosarcoma recently.The prognosis of osteosarcoma is usually unsatisfied.One of the main reasons is that we cannot be able to identify the Achilles heel of osteosarcoma.A growing number of evidence suggests that different types of RNA play various roles in the development of osteosarcoma.The competing endogenous RNA(ceRNA)is a newly emerging theory,which can propose messenger RNA(mRNA),long non-coding RNA(lncRNA),pseudogene and other different transcripts.Therefore,it can play a role in the regulation of microRNA(miRNA)through competition.In the latest researches,it is shown that the interaction of these transcripts play an important role in the occurrence and development of osteosarcoma by mediating biological processes such as proliferation,apoptosis,metastasis and chemotherapy resistance of osteosarcoma cells.In addition,these different types of transcripts may provide new biomarkers and potential therapeutic targets for osteosarcoma.The present studies review the development of ceRNA hypothesis,summarizes existing knowledge system of ceRNA,and develop a systematic review of the role of different types of ceRNA in the pathogenesis and biological function of osteosarcoma.This review could lay the foundation for the basic and clinical study of osteosarcoma and promote the early diagnosis and treatment effects of osteosarcoma.