The human zinc finger (C2H2-type) protein ZNF750 is a transcription factor regulated by p63 that plays a critical role in epithelial tissues homoeostasis, as well as being involved in the pathogenesis of cancer. Indeed, missense mutations, truncation and genomic deletion have been found in oesophageal squamous cell carcinoma. In keeping, we showed that ZNF750 negatively regulates cell migration and invasion in breast cancer cells; in particular, ZNF750 binds and recruits KDM1A and HDAC1 on the LAMB3 and CTNNAL1 promoters. This interaction, in turn, represses the transcription of LAMB3 and CTNNAL1 genes, which are involved in cell migration and invasion. Given that ZNF750 is emerging as a crucial transcription factor that acts as tumour suppressor gene, here, we show that ZNF750 represses the expression of the small GTPase, Ras-related C3 botulinum toxin substrate 1 (RAC1) in breast cancer cell lines, by directly binding its promoter region. In keeping with ZNF750 controlling RAC1 expression, we found an inverse correlation between ZNF750 and RAC1 in human breast cancer datasets. More importantly, we found a significant upregulation of RAC1 in human breast cancer datasets and we identified a direct correlation between RAC1 expression and the survival rate of breast cancer patient. Overall, our findings provide a novel molecular mechanism by which ZNF750 acts as tumour suppressor gene. Hence, we report a potential clinical relevance of ZNF750/RAC1 axis in breast cancer.

人锌指（C2H2型）蛋白ZNF750是受p63调控的转录因子，在上皮组织的同质化中起关键作用，并参与癌症的发病机理。确实，在食道鳞状细胞癌中发现了错义突变，截短和基因组缺失。保持一致，我们表明ZNF750负调节乳腺癌细胞中的细胞迁移和侵袭。尤其是ZNF750在LAMB3和CTNNAL1启动子上结合并募集KDM1A和HDAC1 。反过来，这种相互作用抑制了LAMB3和CTNNAL1的转录基因，参与细胞迁移和入侵。鉴于ZNF750逐渐成为一种重要的转录因子，起着抑癌基因的作用，在这里，我们证明ZNF750通过直接抑制乳腺癌细胞系中小GTPase，Ras相关的C3肉毒杆菌毒素底物1（RAC1）的表达。结合其启动子区域。为了与控制RAC1表达的ZNF750保持一致，我们在人乳腺癌数据集中发现ZNF750和RAC1之间存在负相关。更重要的是，我们在人类乳腺癌数据集中发现了RAC1的上调，并且确定了RAC1表达与乳腺癌患者的生存率之间存在直接的相关性。总的来说，我们的发现提供了一种新的分子机制，通过该机制，ZNF750可以作为抑癌基因。因此，