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癌症研究
生物
癌基因
癌变
癌症干细胞
结直肠癌
转录因子
转移
连环素
干细胞
下调和上调
SOX2
癌症
脱氮酶
细胞周期
泛素
信号转导
细胞生物学
基因
遗传学
作者
Dazhuang Miao,Yan Wang,Yongyi Jia,Jinxue Tong,Shuang Jiang,Lixiu Liu
标识
DOI:10.1016/j.cellsig.2021.110200
摘要
The pathogenesis of colorectal cancer (CRC) is a multistep process characterized by the accumulation of gene mutations and epigenetic alterations. Tumor necrosis factor receptor-associated factor-binding protein domain (ZRANB1) is a deubiquitinase that mediates tumor growth and metastasis by deubiquitinating target proteins. In this study, we examined the regulatory effects of ZRANB1 on the maintenance of cancer stem cell (CSC) properties and tumor growth in CRC. Human CRC tissue samples and matched normal tissues were collected for the analysis of ZRANB1 expression. ZRANB1 was upregulated in CRC human tissues and cell lines, and its expression was positively correlated with advanced tumor stage and poor survival of CRC patients. The overexpression of ZRANB1 also induced the expression of CSC markers in CRC cells. Then, a xenograft model was established by inoculating BALB/c mice with CRC cells. The upregulation of ZRANB1 promoted tumorigenesis in vivo. Sox9 is a transcription factor that acts as an oncogene in human cancers. ZRANB1 increased the stability of Sox9 in CRC cells by decelerating its ubiquitination. Further analysis revealed that Sox9 regulated the transcription activity of USP22 by binding to its promoter. Moreover, ZRANB1 enhances stem-cell-like features of CRC cells and activated the Wnt/β-catenin pathway through USP22. Our results highlighted the role of ZRANB1 as a molecular target for CRC treatment, which may contribute to the development of novel therapies with better efficacy.
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