生物
癌症研究
癌变
基因沉默
基因敲除
DNA损伤
六氯环己烷
细胞周期检查点
癌症
细胞生长
细胞周期
肝癌
支票1
下调和上调
肝细胞癌
细胞凋亡
基因
DNA
遗传学
作者
Xiaozhi Lu,Qian Zhang,Jiahao Xue,Matthias Evert,Diego F. Calvisi,Xin Chen,Xue Wang
标识
DOI:10.1093/toxsci/kfae126
摘要
Abstract Mitotic arrest deficient 2 like 1 (MAD2L1) is a component of the mitotic spindle assembly checkpoint implicated in cancer cell proliferation and tumorigenesis. The functional role of MAD2L1 in hepatocellular carcinoma (HCC) has not been adequately investigated, especially in vivo. In the current manuscript, we sought to address the function of MAD2L1 in hepatocarcinogenesis. We found that MAD2L1 expression is upregulated in human HCCs, where its expression is associated with higher aggressive tumor grade, elevated proliferative activity, and poor prognosis. In human HCC cell lines, MAD2L1 knockdown led to decreased cell growth. Moreover, RNA-seq results demonstrated that MAD2L1 silencing induces the expression of genes associated with cell cycle, DNA replication, and various cancer-related pathways, supporting the critical role of MAD2L1 during HCC growth and differentiation. In a c-MYC-induced mouse HCC model, we revealed an increased expression of Mad2l1. Furthermore, Mad2l1 CRIPSR-mediated silencing prevented c-MYC-driven mouse liver development. Altogether, our study suggests that MAD2L1 plays a crucial role in hepatocarcinogenesis, and that its suppression could be a promising therapeutic strategy for treating human HCC.
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