School of Life Sciences, The Engineering Research Center of Sustainable Development and Utilization of Biomass Energy, Yunnan Normal University, Kunming, Yunnan, 650500, China.
State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai, 200433, China.
Mutat Res Rev Mutat Res. 2019 Jan-Mar;779:1-35. doi: 10.1016/j.mrrev.2018.11.001. Epub 2018 Nov 23.
Micronuclei (MN), the small nucleus-like bodies separated from the primary nucleus, can exist in cells with numerical and/or structural chromosomal aberrations in apparently normal tissues and more so in tumors in humans. While MN have been observed for over 100 years, they were merely and constantly considered as passive indicators of chromosome instability (CIN) for a long time. Relatively little is known about the molecular origins and biological consequences of MN. Rapid technological advances are helping to close these gaps. Very recent studies provide exciting evidence that MN act as key platform for chromothripsis and a trigger of innate immune response, suggesting that MN could affect cellular functions by both genetic and nongenetic means. These previously unappreciated findings have reawakened widespread interests in MN. In this review, the diverse mechanisms leading to MN generation and the complex fate profiles of MN are discussed, together with the evidence for their contribution to CIN, inflammation, senescence and cell death. Moreover, we put this knowledge together into a speculative perspective on how MN may be responsible for cancer development and how their presence may influence the choice of treatment. We suggest that the heterogeneous responses to MN may function physiological to ensure the arrestment, elimination and immune clearance of damaged cells, but pathologically, may enable the survival and oncogenic transformation of cells bearing CIN. These insights not only underscore the complexity of MN biology, but also raise a host of new questions and provide fertile ground for future research.
微核（MN）是从主核中分离出来的小型核样体，存在于具有数量和/或结构染色体畸变的细胞中，在人类的正常组织中更为明显，在肿瘤中更为明显。虽然 MN 已经观察了 100 多年，但它们长期以来一直被认为只是染色体不稳定性（CIN）的被动指标。关于 MN 的分子起源和生物学后果，人们知之甚少。快速的技术进步正在帮助缩小这些差距。最近的研究提供了令人兴奋的证据，表明 MN 作为染色体重排和先天免疫反应的触发因素发挥作用，这表明 MN 可以通过遗传和非遗传手段影响细胞功能。这些以前未被重视的发现重新引起了人们对 MN 的广泛关注。在这篇综述中，讨论了导致 MN 产生的多种机制和 MN 的复杂命运特征，以及它们对 CIN、炎症、衰老和细胞死亡的贡献的证据。此外，我们将这些知识整合到一个关于 MN 如何可能导致癌症发展以及它们的存在如何影响治疗选择的推测性观点中。我们认为，对 MN 的异质反应可能在生理上有助于确保受损细胞的阻滞、消除和免疫清除，但在病理上，可能使携带 CIN 的细胞能够存活和致癌转化。这些见解不仅强调了 MN 生物学的复杂性，而且还提出了一系列新的问题，并为未来的研究提供了肥沃的土壤。
