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RNF114 Interacts with EWSR1 to Regulate VEGFR2 in HER2-positive Breast Cancer
Yingchuan Zhu1, Yue Song1, Yilu Lu1
1Department of Medical Genetics, Frontiers Science Center for Disease-related Molecular Networks, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
Abstract:
RNF114, a member of the E3 ubiquitin ligase family, was first identified as a zinc-binding protein that exhibits frequent genomic amplification across various cancers. Previous studies have shown that inhibition of RNF114 E3 ligase activity by Nimbolide treatment can result in trapping of PARP1 and synthetic lethality in BRCA-mutated cancers, suggesting its E3 ligase role in tumor progress. However, it's important to reveal novel functions and interacting molecules of RNF114. Here, we first described that RNF114 promotes tumor proliferation and autophagy by interacting with EWSR1 and regulating VEGFR2 expression in HER2-positive breast cancer (BC). Our results also showed that RNF114 is significantly overexpressed in BC and is associated with TNM stage and poor prognosis in BC patients. And knockdown of RNF114 suppresses proliferation, migration, invasion, and autophagy of HER2-positive BC cells. Our findings highlight the transcriptional regulatory function of RNF114 in BC, offering new insights into its oncogenic role and contribution to HER2-positive BC progression.
Insights
RNF114, an E3 ubiquitin ligase, drives tumor growth and autophagy in HER2-positive breast cancer by interacting with EWSR1 and regulating VEGFR2. Its overexpression correlates with poor prognosis, highlighting its oncogenic role.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Genetics
Background:
- RNF114 is an E3 ubiquitin ligase amplified in various cancers.
- Previous research linked RNF114 E3 ligase activity to synthetic lethality in BRCA-mutated cancers.
- Novel functions and interacting molecules of RNF114 require elucidation.
Purpose of the Study:
- To investigate the novel functions of RNF114 in HER2-positive breast cancer (BC).
- To identify interacting molecules and downstream targets of RNF114 in BC.
- To explore the role of RNF114 in tumor proliferation, migration, invasion, and autophagy.
Main Methods:
- Investigated RNF114 interactions with EWSR1 and regulation of VEGFR2 expression.
- Assessed RNF114 expression levels in breast cancer patient cohorts.
- Utilized knockdown experiments to evaluate the functional impact of RNF114 on BC cell behavior.
Main Results:
- RNF114 promotes tumor proliferation and autophagy via EWSR1 interaction and VEGFR2 regulation in HER2-positive BC.
- RNF114 is significantly overexpressed in BC, correlating with advanced TNM stage and poor patient prognosis.
- Knockdown of RNF114 suppressed proliferation, migration, invasion, and autophagy in HER2-positive BC cells.
Conclusions:
- RNF114 possesses a transcriptional regulatory function in breast cancer.
- RNF114 plays a significant oncogenic role in the progression of HER2-positive breast cancer.
- RNF114 represents a potential therapeutic target for HER2-positive breast cancer.
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