Ning Wu, Ling Wei, Zhipeng Zhu, Qiang Liu, Kailong Li, Fengbiao Mao, Jie Qiao, Xiaolu Zhao
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引用次数: 0
摘要
染色体外环状脱氧核糖核酸(eccDNA)起源于染色体脱氧核糖核酸(DNA),但不属于染色体脱氧核糖核酸(DNA),它们以环状形式组织,早已在单细胞和多细胞真核生物中发现。人们对它们的生物起源和功能知之甚少,因为它们的特征是序列与线性 DNA 同源,而线性 DNA 的检测方法却很少。最近,高通量测序技术的进步揭示了eccDNA在肿瘤形成、进化、耐药性以及衰老、基因组多样性和其他生物过程中的关键作用,使其再次成为研究热点。目前已提出多种cccDNA形成机制,包括断裂-融合-桥(BFB)和易位-缺失-扩增模型。妇科肿瘤以及胚胎和胎儿发育障碍是人类生殖健康的主要威胁。自首次在猪精子中发现cccDNA和在卵巢癌腹水中发现双分以来,cccDNA在这些病理过程中的作用已被部分阐明。本综述总结了cccDNAs的研究历史、生物发生以及目前可用的检测和分析方法,并阐明了它们在妇科肿瘤和生殖中的功能。我们还提出了将cccDNAs作为药物靶点和液体活检标志物应用于产前诊断和妇科肿瘤的早期检测、预后和治疗的建议。这篇综述为今后研究cccDNAs在重要生理和病理过程中的复杂调控网络奠定了理论基础。
Innovative insights into extrachromosomal circular DNAs in gynecologic tumors and reproduction.
Originating but free from chromosomal DNA, extrachromosomal circular DNAs (eccDNAs) are organized in circular form and have long been found in unicellular and multicellular eukaryotes. Their biogenesis and function are poorly understood as they are characterized by sequence homology with linear DNA, for which few detection methods are available. Recent advances in high-throughput sequencing technologies have revealed that eccDNAs play crucial roles in tumor formation, evolution, and drug resistance as well as aging, genomic diversity, and other biological processes, bringing it back to the research hotspot. Several mechanisms of eccDNA formation have been proposed, including the breakage-fusion-bridge (BFB) and translocation-deletion-amplification models. Gynecologic tumors and disorders of embryonic and fetal development are major threats to human reproductive health. The roles of eccDNAs in these pathological processes have been partially elucidated since the first discovery of eccDNA in pig sperm and the double minutes in ovarian cancer ascites. The present review summarized the research history, biogenesis, and currently available detection and analytical methods for eccDNAs and clarified their functions in gynecologic tumors and reproduction. We also proposed the application of eccDNAs as drug targets and liquid biopsy markers for prenatal diagnosis and the early detection, prognosis, and treatment of gynecologic tumors. This review lays theoretical foundations for future investigations into the complex regulatory networks of eccDNAs in vital physiological and pathological processes.
期刊介绍:
Protein & Cell is a monthly, peer-reviewed, open-access journal focusing on multidisciplinary aspects of biology and biomedicine, with a primary emphasis on protein and cell research. It publishes original research articles, reviews, and commentaries across various fields including biochemistry, biophysics, cell biology, genetics, immunology, microbiology, molecular biology, neuroscience, oncology, protein science, structural biology, and translational medicine. The journal also features content on research policies, funding trends in China, and serves as a platform for academic exchange among life science researchers.