生物
细胞凋亡
细胞生长
泛素连接酶
癌症研究
流式细胞术
免疫印迹
分子生物学
卵巢癌
转染
细胞培养
泛素
癌症
生物化学
基因
遗传学
作者
Yanyan Wang,Shanfeng Wang,Wenjuan Zhang
出处
期刊:Cell Cycle
[Informa]
日期:2023-02-21
卷期号:22 (9): 1116-1126
被引量:5
标识
DOI:10.1080/15384101.2023.2178102
摘要
The E3 ubiquitin ligase 3-hydroxy-3-methylglutaryl reductase degradation (HRD1) was found to be a tumor suppressor in diverse types of cancers; we aimed to explore its expression pattern and biological function in ovarian cancer (OC). HRD1 expression in OC tumor tissues was detected using quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC). The overexpression plasmid of HRD1 was transfected into OC cells. Cell proliferation, colony formation, and apoptosis were analyzed using bromodeoxy uridineassay, colony formation assay, and flow cytometry, respectively. OC mice models were established to explore the effect of HRD1 on OC in vivo. Ferroptosis was evaluated by malondialdehyde, reactive oxygen species, and intracellular ferrous iron. Expressions offerroptosis-related factors were examined using qRT-PCR and western blot. Erastin and Fer-1 were, respectively, employed to promote or inhibit ferroptosis in OC cells. Online bioinformatics tool and co-immunoprecipitation assay were performed to predict and verify the interactive genes of HRD1 in OC cells, respectively. Gain-of-function studies were carried out to determine the roles of HRD1 in cell proliferation, apoptosis, and ferroptosis in vitro. HRD1 was under-expressed in OC tumor tissues. The overexpression of HRD1 inhibited OC cell proliferation and colony formation in vitro and suppressed OC tumor growth in vivo. The overexpression of HRD1 promoted cell apoptosis and ferroptosis in OC cell lines. HRD1 interacted with the solute carrier family 7 member 11 (SLC7A11) in OC cells, and HRD1 regulated the stability and ubiquitination in OC. SLC7A11 overexpression recovered the effect of HRD1 overexpression in OC cell lines. HRD1 inhibited tumor formation and promoted ferroptosis in OC through enhancing SLC7A11 degradation.
科研通智能强力驱动
Strongly Powered by AbleSci AI