免疫印迹
泛素
脱氮酶
组蛋白脱乙酰基酶2
下调和上调
细胞生物学
STAT蛋白
信号转导
癌症研究
生物
化学
分子生物学
组蛋白脱乙酰基酶
车站3
组蛋白
生物化学
基因
作者
Aiping Li,Ting Wang,Shasha Zhou,Jingjing Han,Wujia Wu
出处
期刊:Placenta
[Elsevier]
日期:2024-01-01
卷期号:145: 9-18
标识
DOI:10.1016/j.placenta.2023.11.010
摘要
Ubiquitination is a significant post-translational modification engaged in diverse biological processes, such as cell differentiation, metastasis, and protein stability modulation. The dysregulation of ubiquitination and deubiquitination is inextricably linked to disease progression, including preeclampsia (PE). Ubiquitin-specific protease 17 (USP17), a prominent deubiquitinating enzyme that regulates ubiquitination modifications, performs multiple functions at the cellular level, whereas its role in PE remains elusive. In this study, we intended to probe the role of USP17 in PE and its underlying mechanisms. The USP17 level in the plasma of PE patients was detected through Elisa. Western blot and qRT-PCR were performed to measure the mRNA and protein level of USP17 in placental tissues. CCK-8, EdU, and transwell assays were conducted to evaluate the proliferation, migration, and invasion of trophoblast cells. The interaction between HDAC2 and USP17 or STAT1 were determined by co-immunoprecipitation and Western blot assays. The expression of NF-κB pathway related proteins was examined using Western blot. USP17 was dramatically downregulated in PE patients. Overexpression of USP17 facilitated trophoblast proliferation, migration, and invasion. Moreover, histone deacetylase 2 (HDAC2) was validated as a substrate of USP17 deubiquitination, and USP17 upregulation enhanced HDAC2 protein level. Furthermore, HDAC2 could interact with and deacetylate Signal transducer and activator of transcription 1 (STAT1), resulting in the enhancement of STAT1 activity and inhibition of NF-κB signaling. Our findings disclosed that USP17 augmented the proliferation and invasion of trophoblast by deubiquitinating HDAC2, which will contribute to novel prospective targets for diagnosing and treating PE.
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