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免疫原性微核在肿瘤中的发病机制及研究进展
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Abstract:
在过去的几年中，基因组测序技术的进步已经揭示，由于持续的基因组不稳定性，患者的癌症基因组在患者之间以及个体肿瘤内都是高度异质性的。除了是肿瘤基因组异质性的关键来源之外，染色体错误分离还可能导致基因组物质在有丝分裂后被排除在初级核之外，并被封装到细胞质中的较小核小体中，称为微核(micronuclei, MN)。大量研究显示，具有免疫原性的MN介导了炎症反应、抗肿瘤作用和促癌症转移等下游途径，暗示免疫原性微核(immunogenic micronuclei, iMN)具有广泛的生物医学意义。迄今为止，还没有广泛的综述可以综合研究iMN在肿瘤中的发病机制及研究进展。在这篇综述中，我们旨在总结近年来iMN在分子起源和细胞对iMN的反应方面的进展。我们将首先讨论MN形成的多种分子机制，然后概述iMN与癌症之间的关联，并以新兴的研究课题和挑战结束。本综述将全面了解免疫原性微核在肿瘤中的发病机制及研究进展。
In the past few years, the advancement of genomic sequencing technology has revealed that the cancer genomes of patients are highly heterogeneous between patients as well as within individual tumors due to ongoing genomic instability. In addition to being a key source of tumor genomic heterogeneity, chromosomal missegregation can also result in the exclusion of genomic material from the primary nucleus after mitosis and its encapsulation in smaller nucleosomes in the cytoplasm, known as micronuclei (MN). A large number of studies have shown that immunogenic MN mediates downstream pathways, such as inflammatory responses, antitumor effects, and promotion of cancer metastasis, suggesting that immunogenic micronuclei (iMN) have widespread biomedical significance. To date, there has been no comprehensive review that summarizes the pathogenesis and research progress of iMN in tumors. In this review, we aim to summarize recent advances in molecular origins and cellular responses to iMN. We will first discuss the various molecular mechanisms of MN formation, and then outline the association between iMN and cancer, concluding with emerging research topics and challenges. This review will provide a comprehensive understanding of the pathogenesis and research progress of immunogenic micronuclei in tumors.
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