期刊
CANCER SCIENCE
卷 111, 期 6, 页码 2062-2077出版社
WILEY
DOI: 10.1111/cas.14413
关键词
ASH2L; co-regulator; endometrial cancer; histone methylation; transcription
类别
资金
- National Natural Science Foundation of China [31871286, 81872015, 31701102, 81702800, 81502438, 81902889]
Absent, small or homeotic 2-like protein (ASH2L) is a core component of a multimeric histone methyltransferase complex that is involved in the maintenance of active transcription, participating in several cancers, however the biological function and molecular mechanism of ASH2L in endometrial cancer (ECa) are largely unknown. Endometrial cancer is a common malignant tumor in women and the incidence of this cancer is on the rise. Estrogen-ER alpha signaling, as an oncogenic pathway, plays a crucial role in endometrial carcinogenesis. Therefore, further exploration of the molecular mechanisms around ER alpha-mediated gene transcription in ECa would be helpful to the understanding of tumor development and to finding a new therapeutic target for ECa. Here, our study demonstrated that ASH2L was highly expressed in ECa samples, and higher expression of ASH2L was positively correlated with a poor prognosis. Moreover, we identified that ASH2L associated with ER alpha and that knockdown of ASH2L resulted in decreased expression of a subset of the estrogen-induced target genes, including paired box 2 (PAX2), an oncogenic gene in ECa. ASH2L was recruited to cis-regulatory elements in PAX2, thereby altering histone H3K4me3 and H3K27me3 levels, to enhance ER alpha-mediated transactivation. Finally, depletion of ASH2L suppressed endometrial cancer cell proliferation and migration. Our findings suggest that ASH2L participates in the promotion of ECa progression, if not totally at least partially, via upregulation of PAX2 transcription.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据