微核普遍存在于肿瘤细胞。衰老分泌表型(SASP)是近年来发现的与细胞衰老相关的重要调节机制，可以诱导癌细胞基因组不稳定及肿瘤微环境改变而促进肿瘤恶性表型。SASP活化主要由cGAS结合胞浆游离DNA而触发，而微核及相关自噬可能是癌细胞激活SASP的主要途径。乙酰化酶NAT10具有调节细胞核仁、分裂、细胞骨架等多种功能。我们已经证明NAT10与结直肠癌生物学特性具有重要关系，同时在新近研究中又发现NAT10普遍存在于癌细胞微核、与自噬相关蛋白形成核自噬体而激活cGAS，而NAT10抑制剂Remodelin或基因敲除均可降低癌细胞微核、核自噬、及cGAS活化，提示NAT10与SASP调节机制具有重要联系。因此，拟以结直肠癌为对象进一步阐明NAT10对微核、核自噬、SASP的调节作用和机制，确定NAT10微核激活SASP机制对结直肠癌生物学特性的调节作用，并探讨其在结肠癌临床治疗中的应用。

Micronuclei is generally detected in most of cancer cells. SASP (Senescence associated secretory phenotype) is a cell senescence-associated regulatory machinery under extensively investigation in current. Through either autocrine or paracrine way, SASP could induce cell senescence and promotes production of pro-inflammatory factors, which prove subsequently causing genomic instability of cancer cells and remodeling of tumor microenvironment, resulting in tumor progression. It has been recently demonstrated that SASP could be triggered by the binding of cGAS(cyclic GMP-AMP synthase) to free DNA in cytosol with resultant production of the second messenger 2,3-cyclic GMP-AMP, which activates STING(Stimulator interferon of gene) and its downstream genes. Nucleophagy formed from micronuclei of cancer cells is considered to be the main source of cytoplasmic DNA. Therefore, elucidation of SASP activation by micronuclei and related nucleophagy in cancer cells could be important to cancer development and therapeutic treatment. N-acetyltransferase 10(NAT10) has been identified to regulate the activities of cellular nucleolus, cytokinesis and cytoskeleton remodeling. We have also revealed that NAT10 could regulate biological activities of colorectal cancers, and beyond, recently we have discovered that NAT10 does usually localize in micronuclei in most of cancer cells, and subsequently co-localizes with the key factors responsible for autophagy such as LC3, SQSTM1, LAMP2 to form nucleophagy, and probably also interacts with cGAS. The treatment of Remodelin, a NAT10 inhibitor, or genomic deletion of NAT10 by CRISPR/Cas9 could reduce markedly the formation of NAT10 micronuclei, nucleophagy and interaction with cGAS, indicating that NAT10 could be involved in regulation of micronuclei, nucleophagy and SASP activation. Thus, the proposal is to plane to get insight of the molecular mechanism about the involvement of NAT10 in the formation of micronuclei and nucleophagy as well as SASP activation, and then to clarify NAT10-related SASP on the regulation of biological activity of colorectal cancers, and further to explore the applicable potentials in clinic treatment of colorectal cancers.