Wnt信号通路
永恒的
生物
基因敲除
癌症研究
细胞生长
细胞生物学
转录因子
肿瘤进展
信号转导
癌症
基因
昼夜节律
遗传学
内分泌学
作者
Zhaoxia Wang,Simin He,Lingbiao Xin,Ying Zhou,Le Zhao,Fuyuan Wang
标识
DOI:10.1016/j.cellsig.2024.111045
摘要
TIMELESS (TIM) is a circadian gene which is implicated in the regulation of daily rhythm, DNA replication and repair, and cancer initiation and progression. Nevertheless, the role of TIM in endometrial cancer (EC) development is largely unknown. Bioinformatics analysis showed that TIM was aberrantly up-regulated in EC tissues and positively correlated with clinical or histological grade of EC. Functional studies showed that TIM knockdown reduced EC cell viability and restrained EC cell migration in vitro, as well as blocked xenograft tumor growth in vivo. Mechanistically, HMGB1 transcriptionally up-regulated TIM expression in EC cells. In addition, TIM could activate the transcription of the canonical Wnt ligand WNT8B, and TIM depletion could reduce the malignant potential of EC cells largely by targeting and down-regulating WNT8B. As a conclusion, HMGB1/TIM/WNT8B signal cascade was identified in this study for the first time. HMGB1 exerted its oncogenic role by activating the transcription of TIM, leading to the activation of Wnt signaling and EC progression.
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