2. Academic Validation
  3. NANOG regulate the JAK/STAT3 pathway to promote trophoblast cell migration and epithelial-mesenchymal transition (EMT) in hypertensive disorders of pregnancy (HDP) through protein interaction with CDK1

NANOG regulate the JAK/STAT3 pathway to promote trophoblast cell migration and epithelial-mesenchymal transition (EMT) in hypertensive disorders of pregnancy (HDP) through protein interaction with CDK1

  • Am J Reprod Immunol. 2024 May;91(5):e13863. doi: 10.1111/aji.13863.
Jing Ma 1,  Mingchang Liu 2 3,  Zhuo Chen 4,  Shiyang Liu 3,  Huijuan Yang 4,  Mengjia Duan 4
Affiliations

Affiliations

  • 1 Department of Reproduction and Genetics, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China.
  • 2 Yunnan Maternal and Child Health Care Hospital, Kunming, Yunnan, China.
  • 3 Kunming Medical University, Kunming, Yunnan, China.
  • 4 Department of Obstetrics and Gynecology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China.
PMID: 38796740 DOI: 10.1111/aji.13863
Abstract

Problem: Hypertensive disorders of pregnancy (HDP) are a common pregnancy disease. NANOG and Cyclin-dependent kinase 1 (CDK1) are essential for regulating the function of cell proliferation and Apoptosis. However, the mechanism of action in HDP is yet unclear.

Method: The microarray dataset GSE6573 was downloaded from the GEO database. Emt-related gene set was downloaded from Epithelial-Mesenchymal Transition gene database 2.0 were screened differentially expressed genes by bioinformatics analysis. Pathway Commons and Scansite 4.0 databases were used to predict the interaction between proteins. Placental tissue samples were collected from HDP patients and patients with uneventful pregnancies. RT-qPCR, Western blot and immunohistochemistry were used to detect the expression of NANOG, CDK1, MMP-2, MMP-9, EMT markers and the JAK/STAT3 pathway proteins. Transfection NANOG overexpression/knockdown, and CDK1 knockdown into the human chorionic trophoblast cells (HTR-8/Svneo). CCK-8, Transwell and Wound-healing assay were used to evaluate cell proliferation, invasion and migration. CO-IP and GST pull-down assays were used to confirm the protein interaction.

Results: A total obtained seven EMT-related differentially expressed genes, wherein NANOG, NODAL and LIN28A had protein interaction. In the HDP patients' tissue found that NANOG and CDK1 had lower expression. NANOG overexpression promoted HTR-8/Svneo proliferation, migration and EMT, while NANOG knockdown had the opposite effect. Further a protein interaction between STAT3 and CDK1 with NANOG. NANOG overexpression downregulated the JAK/STAT3 pathway to promote HTR-8/Svneo proliferation, migration and EMT, which was reversed by CDK1 knockdown.

Conclusions: NANOG downregulated the JAK/STAT3 pathway to promote trophoblast cell proliferation, migration and EMT through protein interaction with CDK1.

Keywords

JAK/STAT3 pathway; NANOG; cyclin‐dependent kinase 1 (CDK1); epithelial‐mesenchymal transition (EMT); hypertensive disorders of pregnancy (HDP).

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