六氯环己烷
肝细胞癌
癌变
超极化(物理学)
抑制器
生物
核苷酸
内科学
癌症研究
基因剔除小鼠
内分泌学
化学
医学
基因
癌症
遗传学
核磁共振波谱
有机化学
作者
Yueqi Zhang,Xinhui Liu,Kairui Sun,Yang Luo,Jack Yang,Aimin Li,Matti Kiupel,Stefanie Fenske,Martin Biel,Qing‐Sheng Mi,Hongbing Wang,Haifeng Xiao
出处
期刊:Cell Reports
[Elsevier]
日期:2023-10-01
卷期号:42 (10): 113157-113157
被引量:1
标识
DOI:10.1016/j.celrep.2023.113157
摘要
Summary
Sex differences in hepatocellular carcinoma (HCC) development are regulated by sex and non-sex chromosomes, sex hormones, and environmental factors. We previously reported that Ncoa5+/− mice develop HCC in a male-biased manner. Here we show that NCOA5 expression is reduced in male patient HCCs while the expression of an NCOA5-interacting tumor suppressor, TIP30, is lower in female HCCs. Tip30 heterozygous deletion does not change HCC incidence in Ncoa5+/− male mice but dramatically increases HCC incidence in Ncoa5+/− female mice, accompanied by hepatic hyperpolarization-activated cyclic nucleotide-gated cation channel 3 (HCN3) overexpression. HCN3 overexpression cooperates with MYC to promote mouse HCC development, whereas Hcn3 knockout preferentially hinders HCC development in female mice. Furthermore, HCN3 amplification and overexpression occur in human HCCs and correlate with a poorer prognosis of patients in a female-biased manner. Our results suggest that TIP30 and NCOA5 protect against female liver oncogenesis and that HCN3 is a female-biased HCC driver.
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