妇科肿瘤与生殖领域中外源环状 DNA 的创新见解。

Innovative insights into extrachromosomal circular DNAs in gynecologic tumors and reproduction.

机构信息

State Key Laboratory of Female Fertility Promotion, Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Center for Reproductive Medicine, Peking University Third Hospital, Beijing 100191, China.

National Clinical Research Center for Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China.

出版信息

Protein Cell. 2024 Jan 3;15(1):6-20. doi: 10.1093/procel/pwad032.

Abstract

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.

摘要

起源于染色体但不含染色体 DNA 的染色体外环状 DNA(eccDNA)以环状形式存在,长期以来一直存在于单细胞和多细胞真核生物中。由于它们与线性 DNA 具有序列同源性,而针对线性 DNA 的检测方法很少,因此其生物发生和功能仍知之甚少。高通量测序技术的最新进展表明,eccDNA 在肿瘤形成、进化和耐药性以及衰老、基因组多样性和其他生物过程中发挥着关键作用,使其重新成为研究热点。已经提出了几种 eccDNA 形成的机制,包括断裂-融合-桥(BFB)和易位缺失扩增模型。妇科肿瘤和胚胎及胎儿发育障碍是人类生殖健康的主要威胁。自从在猪精子中首次发现 eccDNA 和卵巢癌腹水中的双微体以来,eccDNA 在这些病理过程中的作用部分得到了解释。本综述总结了 eccDNA 的研究历史、生物发生以及目前用于 eccDNA 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 eccDNA 作为药物靶点和液体活检标志物用于产前诊断以及妇科肿瘤的早期检测、预后和治疗的建议。本综述为未来研究 eccDNA 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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b010/10762679/efde75c7cc66/pwad032_fig1.jpg

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