MORC家族CW型锌指4（MORC4）具有核基质结合域，已被观察到参与多种癌症发展。通过挖掘三个基因表达芯片（GSE110223、GSE110224和GSE24514），我们发现MORC4在结直肠癌（CRC）样本中过度表达（log2倍变化>1，p<0.05）。我们旨在研究MORC4在CRC恶性行为中的作用，重点关注多聚编码组环指1（PCGF1）/细胞分裂素依赖性激酶抑制因子1A（CDKN1A）轴。首先，我们确认MORC4是60对冻存CRC和相邻正常样本中的上调基因。MORC4过表达增加了SW480和HT29细胞的增殖和转移，并降低了细胞凋亡，这种效应可以通过转录抑制剂PCGF1（一个强效细胞周期蛋白依赖性激酶抑制剂CDKN1A的转录抑制剂）的敲低来减弱。通过共免疫沉淀，MORC4进一步被确定为与PCGF1相互作用的新型分子。MORC4本身并未实质性地抑制CDKN1A的转录活性，但它增强了PCGF1对CDKN1A的影响。此外，MORC4作为HECT、C2和WW域含有E3泛素蛋白连接酶2（HECW2）的底物，并通过泛素-蛋白酶体系统降解。总之，我们的研究表明，MORC4通过控制PCGF1/CDKN1A信号加速CRC进展。©2023. 作者，独家许可Springer Nature America，Inc.

MORC family CW-type zinc finger 4 (MORC4) possessing nuclear matrix binding domains has been observed to be involved in multiple cancer development. By digging three gene expression omnibus (GEO) gene microarrays (GSE110223, GSE110224 and GSE24514), we found that MORC4 was overexpressed in colorectal cancer (CRC) samples (log2 Fold change >1, p < 0.05). We aimed to investigate the role of MORC4 in CRC malignant behaviors, with an emphasis on polycomb group ring finger 1 (PCGF1)/cyclin-dependent kinase inhibitor 1A (CDKN1A) axis. Firstly, we confirmed MORC4 as an upregulated gene in 60 pairs of frozen CRC and adjacent normal samples. MORC4 overexpression increased proliferation and metastasis, and decreased apoptosis in SW480 and HT29 cells, which was diminished by the knockdown of PCGF1, a transcriptional repressor of CDKN1A (a potent cyclin-dependent kinase inhibitor). MORC4 was further identified as a novel molecule that interacted with PCGF1 via coimmunoprecipitation. MORC4 itself did not substantially suppress CDKN1A transcriptional activity, but it augmented PCGF1's effect on CDKN1A. Additionally, MORC4 acted as the substrate of HECT, C2, and WW domain-containing E3 ubiquitin protein ligase 2 (HECW2) and was degraded through ubiquitin-proteasome system. Collectively, our work suggested that MORC4 accelerated CRC progression via governing PCGF1/CDKN1A signaling.© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.