结直肠癌（CRC）已成为全球健康问题，其在所有类型的癌症中几乎具有最高的患病率和死亡率。本研究旨在揭示MCM8在CRC发展和进展过程中的生物学功能和潜在机制。发现MCM8在CRC组织中的表达水平升高，并与肿瘤分级和患者生存率显著相关。在体外实验中，抑制CRC细胞中MCM8的表达可以抑制细胞生长和细胞活动性，同时促进细胞凋亡，并且在异种移植小鼠模型中抑制肿瘤生长。基于对具有或无MCM8敲除的CRC细胞进行的RNA筛选及随后的IPA分析，发现CHSY1是MCM8在CRC中的潜在靶标，其在肿瘤组织中的表达也高于正常组织。此外，证明MCM8可能通过影响其NEDD4介导的泛素化来调节CHSY1的表达，二者协同对CRC产生肿瘤促进效应。总之，本研究的结果首次表明MCM8在CRC中起到肿瘤促进作用，并可能成为CRC治疗的有希望的治疗靶点。© 2023. BioMed Central Ltd., part of Springer Nature.

Colorectal cancer (CRC) has become a global health problem which has almost highest morbidity and mortality in all types of cancers. This study aimed to uncover the biological functions and underlying mechanism of MCM8 in the development and progression of CRC. The expression level of MCM8 was found to be upregulated in CRC tissues and significantly associated with tumor grade and patients' survival. Knocking down MCM8 expression in CRC cells could restrain cell growth and cell motility while promoting cell apoptosis in vitro, as well as inhibit tumor growth in xenograft mice model. Based on the RNA screening performing on CRC cells with or without MCM8 knockdown and the following IPA analysis, CHSY1 was identified as a potential target of MCM8 in CRC, whose expression was also found to be higher in tumor tissues than in normal tissues. Moreover, it was demonstrated that MCM8 may regulate the expression of CHSY1 through affecting its NEDD4-mediated ubiquitination, both of which synergistically execute tumor promotion effects on CRC. In conclusion, the outcomes of our study showed the first evidence that MCM8 act as a tumor promotor in CRC, and may be a promising therapeutic target of CRC treatment.© 2023. BioMed Central Ltd., part of Springer Nature.