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Screening Preeclampsia Genes and the Effects of CITED2 on Trophoblastic Function
Xiujing Lu1, Xi Lan1, Xiaoqian Fu1
1Department of Obstetrics and Gynecology, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, People's Republic of China.
Insights
CBP/p300-interacting transactivator with glutamic acid/aspartic acid-rich carboxyl-terminal domain 2 (CITED2) is upregulated in preeclampsia (PE) placentas and affects trophoblast function, suggesting it as a potential therapeutic target for PE.
Area of Science:
- Obstetrics and Gynecology
- Molecular Biology
- Genetics
Background:
- Preeclampsia (PE) is a significant obstetric complication with unclear mechanisms.
- Dysregulation of CBP/p300-interacting transactivator with glutamic acid/aspartic acid-rich carboxyl-terminal domain 2 (CITED2) is implicated in various disorders.
- The specific role of CITED2 in PE pathogenesis remains largely unknown.
Purpose of the Study:
- To identify hub genes associated with preeclampsia.
- To investigate the role of CITED2 in trophoblast cells using bioinformatic and experimental approaches.
Main Methods:
- Bioinformatic analysis of Gene Expression Omnibus (GEO) datasets to identify PE-related hub genes.
- Immune infiltration and enrichment analyses to determine related pathways and immune cells.
- Validation of CITED2 mRNA and protein levels in PE placentas via PCR and Western Blot (WB).
- In vitro functional assays using siRNA to knockdown CITED2 in trophoblast cells.
Main Results:
- Six PE-related genes were enriched in NOTCH signaling pathways, glycolysis, and hypoxia.
- Immune infiltration analysis indicated a role for activated NK cells and regulatory T cells.
- CITED2 expression was significantly upregulated in PE placentas.
- Knockdown of CITED2 impaired trophoblast cell migration, invasion, and proliferation, while enhancing apoptosis.
Conclusions:
- CITED2 plays a crucial role in regulating trophoblast cell function.
- CITED2 is a potential therapeutic target for managing preeclampsia.
Purpose:
Preeclampsia (PE) is a serious complication of obstetrics and represents a significant challenge in terms of understanding its underlying mechanism. It has been shown that a number of disorders involve dysregulation of the CBP/p300-interacting transactivator with glutamic acid/aspartic acid-rich carboxyl-terminal domain 2 (CITED2). However, the relationship between PE and CITED2 is still mostly unclear. This work aimed to confirm the hub genes linked to PE and explore the roles of CITED2 in trophoblast using experimental and bioinformatic methods.
Methods:
To determine the hub genes, bioinformatics research was performed on two datasets from the Gene Expression Omnibus (GEO) public database. Immune infiltration analysis and enrichment analysis were also used to identify the related pathways and immune cells. PCR and WB were then used to validate the mRNA and protein levels of CITED2 in the PE samples. Finally, the expression of CITED2 was knocked down using siRNA to investigate the function of CITED2 in trophoblast development in vitro.
Results:
The study's findings showed that the NOTCH signaling pathways, glycolysis, and hypoxia were the main areas of enrichment for the six PE-related genes that were tested. The results of immune infiltration suggest that activated NK cells and regulatory T cells may play an important role in this process. CITED2 was significantly upregulated in the PE placenta. In functional tests, the knockdown of CITED2 may enhance apoptosis while suppressing migration, invasion, and proliferation of cells.
Conclusion:
This study offers important proof that CITED2 influences trophoblast cell function and may one day be a therapeutic target for PE.
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