Yonsei Med J.  2022 Jun;63(6):554-563. 10.3349/ymj.2022.63.6.554.

RAR-Related Orphan Receptor: An Accelerated Preeclampsia Progression by Activating the JAK/STAT3 Pathway

• Yu Y
• Zhu T

• KMID: 2530376
• DOI: http://doi.org/10.3349/ymj.2022.63.6.554

Abstract

Purpose
To investigate the effect and underlying mechanism of RAR related orphan receptor A (RORA) on preeclampsia (PE).
Materials and Methods
Differentially expressed genes (DEGs) in four datasets were obtained by using the Venn diagram method. RORA mRNA and protein expressions were detected by qRT-PCR, western blot, and immunohistochemistry. HTR-8/SVneo cell viability, proliferation, invasion, migration, and angiogenesis were detected by CCK-8 assay, EdU assay, Transwell, wound healing assay, and tube formation assay, respectively. The concentration of Ang-1 in cells was assessed using available ELISA kit.Epithelial-mesenchymal transition, proliferation, and angiogenesis-related proteins were detected by western blot. GSEA analysis were performed for common DEGs, and the expression of enriched pathway-related proteins was also detected.
Results
The expression of RORA was increased in PE tissue and HTR-8/SVneo cells. Silencing RORA could promote the migration, invasion, epithelial-mesenchymal transition, proliferation, and angiogenesis of hypoxia-treated HTR-8/SVneo cells. Mechanistically, RORA contributed to the deterioration of PE by activating the JAK2/STAT3 signaling pathway to promote cell proliferation, migration, invasion, and angiogenesis.
Conclusion
RORA was up-regulated in PE and affected HTR-8/SVneo cell proliferation, invasion, migration, apoptosis, and angiogenesis via the JAK2/STAT3 signaling pathway. This provided a novel strategy for the prevention and treatment of PE.

Keyword

Preeclampsia; RAR related orphan receptor A; JAK2/STAT3 signaling pathway; HTR-8/SVneo cells