环状RNA综述及其在癌症中作用的新见解
Review on circular RNAs and new insights into their roles in cancer.
作者信息
Tang Xiaozhu, Ren Hongyan, Guo Mengjie, Qian Jinjun, Yang Ye, Gu Chunyan
机构信息
The Third Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210001, China.
School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China.
出版信息
Comput Struct Biotechnol J. 2021 Jan 22;19:910-928. doi: 10.1016/j.csbj.2021.01.018. eCollection 2021.
Circular RNAs (circRNAs) are a very interesting class of conserved single-stranded RNA molecules derived from exonic or intronic sequences by precursor mRNA back-splicing. Unlike canonical linear RNAs, circRNAs form covalently closed, continuous stable loops without a 5'end cap and 3'end poly(A) tail, and therefore are resistant to exonuclease digestion. The majority of circRNAs are highly abundant, and conserved across different species with a tissue or developmental-stage-specific expression. circRNAs have been shown to play important roles as microRNA sponges, regulators of gene splicing and transcription, RNA-binding protein sponges and protein/peptide translators. Emerging evidence reveals that circRNAs function in various human diseases, particularly cancers, and may function as better predictive biomarkers and therapeutic targets for cancer treatment. In consideration of their potential clinical relevance, circRNAs have become a new research hotspot in the field of tumor pathology. In the present study, the current understanding of the biogenesis, characteristics, databases, research methods, biological functions subcellular distribution, epigenetic regulation, extracellular transport and degradation of circRNAs was discussed. In particular, the multiple databases and methods involved in circRNA research were first summarized, and the recent advances in determining the potential roles of circRNAs in tumor growth, migration and invasion, which render circRNAs better predictive biomarkers, were described. Furthermore, future perspectives for the clinical application of circRNAs in the management of patients with cancer were proposed, which could provide new insights into circRNAs in the future.
环状RNA(circRNAs)是一类非常有趣的保守单链RNA分子,通过前体mRNA反向剪接从前体mRNA外显子或内含子序列衍生而来。与典型的线性RNA不同,circRNAs形成共价闭合、连续稳定的环,没有5'端帽和3'端聚(A)尾,因此对外切核酸酶消化具有抗性。大多数circRNAs高度丰富,在不同物种间保守,具有组织或发育阶段特异性表达。circRNAs已被证明作为微小RNA海绵、基因剪接和转录的调节因子、RNA结合蛋白海绵以及蛋白质/肽翻译器发挥重要作用。新出现的证据表明,circRNAs在各种人类疾病,尤其是癌症中发挥作用,并且可能作为更好的预测生物标志物和癌症治疗的靶点。鉴于其潜在的临床相关性,circRNAs已成为肿瘤病理学领域的一个新的研究热点。在本研究中,讨论了目前对circRNAs的生物发生、特征、数据库、研究方法、生物学功能、亚细胞分布、表观遗传调控、细胞外运输和降解的理解。特别是,首先总结了circRNA研究中涉及的多个数据库和方法,并描述了确定circRNAs在肿瘤生长、迁移和侵袭中的潜在作用的最新进展,这些进展使circRNAs成为更好的预测生物标志物。此外,还提出了circRNAs在癌症患者管理中的临床应用的未来前景,这可能为未来circRNAs的研究提供新的见解。