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Updated: Aug 12, 2025
Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer
Published on: January 12, 2020
Histone methyltransferase SETD1A interacts with notch and promotes notch transactivation to augment ovarian cancer
Hongjuan Chai1, Chunpeng Pan2, Mingyang Zhang3
1Department of Gynecology and Obstetrics, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China.
Background:
High expression of SETD1A, a histone methyltransferase that specifically methylates H3K4, acted as a key oncogene in several human cancers. However, the function and underlying molecular mechanism of SETD1A in ovarian cancer (OV) remain markedly unknown.
Methods:
The expression of SETD1A in OV were detected by Western blot and analyzed online, and the prognosis of STED1A in OV were analyzed online. The protein and mRNA levels were determined by Western blot and RT-qPCR. The cell proliferatin, migration and invasion were measured by CCK-8 and transwell assays. The protein interaction was detected by co-IP assay. The interaction between protein and DNA was performed by ChIP assay. The tumor growth in vivo was performed by xenograft tumor model.
Results:
SETD1A was overexpressed in OV and a predictor of poor prognosis. Overexpression of SETD1A augmented the abilities of cell proliferation, migration, and invasion in MRG1 and OVCAR5 cells. In comparison, SETD1A knockdown suppressed cell growth, migration, and invasion in SKOV3 and Caov3 cells. Specifically, SETD1A enhanced Notch signaling by promoting the expression of Notch target genes, such as Hes1, Hey1, Hey2, and Heyl. Mechanistically, SETD1A interacted with Notch1 and methylated H3K4me3 at Notch1 targets to enhance Notch signaling. In addition, restoration of Notch1 in SETD1A-knockdown OV cells recovered cell proliferation, migration and invasion, which was inhibited by SETD1A knockdown. Furthermore, reduction of SETD1A suppressed tumorigenesis in vivo.
Conclusion:
In conclusion, our results highlighted the key role of SETD1A in OV development and proved that SETD1A promotes OV development by enhancing Notch1 signaling, indicating that SETD1A may be a novel target for OV treatment.
Insights
SETD1A is overexpressed in ovarian cancer (OV), promoting tumor growth and poor prognosis by enhancing Notch1 signaling. Targeting SETD1A may offer a new therapeutic strategy for OV treatment.
Area of Science:
- Oncology
- Molecular Biology
- Epigenetics
Background:
- SETD1A, a histone methyltransferase, is a known oncogene in various cancers.
- Its role and mechanism in ovarian cancer (OV) remain largely uncharacterized.
Purpose of the Study:
- To investigate the function and molecular mechanism of SETD1A in ovarian cancer.
- To determine if SETD1A is a potential therapeutic target for OV.
Main Methods:
- Assessed SETD1A expression and prognosis in OV using Western blot and online analysis.
- Evaluated cell proliferation, migration, and invasion via CCK-8 and Transwell assays.
- Investigated protein interactions (co-IP), DNA binding (ChIP), and in vivo tumor growth (xenograft model).
Main Results:
- SETD1A is overexpressed in OV, correlating with poor prognosis.
- SETD1A promotes OV cell proliferation, migration, and invasion by enhancing Notch signaling via H3K4me3 methylation at Notch1 targets.
- SETD1A knockdown suppressed tumor growth in vivo, while Notch1 restoration reversed these effects.
Conclusions:
- SETD1A plays a critical role in OV development by upregulating Notch1 signaling.
- SETD1A represents a promising novel therapeutic target for ovarian cancer.
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