结直肠癌（CRC）仍然是全球癌症死亡的主要原因。因此，识别疾病发病机制的异常基因和蛋白质对于改进早期检测方法和开发新的治疗策略至关重要。染色体不稳定性 (CIN) 或染色体互补体的持续变化是基因组不稳定性的主要形式。它是约 85% 的 CRC 中发现的遗传异质性的驱动因素。尽管 CIN 与 CRC 发病机制有关，但 CIN 背后的分子决定因素仍然知之甚少。最近，F-box 蛋白 EMI1 被确定为候选 CIN 基因。在本研究中，我们试图确定 EMI1 表达减少对 CIN 和细胞转化的影响。将基于 siRNA 的沉默和 CRISPR/Cas9 敲除克隆与定量成像显微镜耦合，我们评估了 EMI1 表达减少对 CIN 和细胞转化的影响定量成像显微镜数据显示，EMI1 表达减少会导致瞬时 (siRNA) 和组成型 (CRISPR/Cas9) 细胞模型中 CIN 表型增加，这些模型与长期 DNA 损伤和细胞转化表型的增加相关研究。这项研究确定，EMI1 表达减少会诱导 CIN 并促进细胞转化，这与早期 CRC 发展中的作用一致。© 2024。作者。

Colorectal cancer (CRC) is still a leading cause of cancer deaths worldwide. Thus, identifying the aberrant genes and proteins underlying disease pathogenesis is critical to improve early detection methods and develop novel therapeutic strategies. Chromosome instability (CIN), or ongoing changes in chromosome complements, is a predominant form of genome instability. It is a driver of genetic heterogeneity found in ~85% of CRCs. Although CIN contributes to CRC pathogenesis, the molecular determinants underlying CIN remain poorly understood. Recently, EMI1, an F-box protein, was identified as a candidate CIN gene. In this study, we sought to determine the impact reduced EMI1 expression has on CIN and cellular transformation.Coupling siRNA-based silencing and CRISPR/Cas9 knockout clones with quantitative imaging microscopy we evaluated the impact reduced EMI1 expression has on CIN and cellular transformation in four colonic epithelial cell contexts.Quantitative imaging microscopy data revealed that reduced EMI1 expression induces increases in CIN phenotypes in both transient (siRNA) and constitutive (CRISPR/Cas9) cell models that are associated with increases in DNA damage and cellular transformation phenotypes in long-term studies.This study determined that reduced EMI1 expression induces CIN and promotes cellular transformation, which is consistent with a role in early CRC development.© 2024. The Author(s).