CircRNA_06354 might promote early-onset preeclampsia in humans via hsa-miR-92a-3p/vascular endothelial growth factor-A

Abstract

Background: Early-onset preeclampsia (EOPE) is a serious pregnancy disorder with multisystem complications. Recently, circRNA was reported to participate in the progression of EOPE. However, the role and mechanism of circRNA_06354 in the pathophysiological development of EOPE remain unclear.

Methods: Blood samples from patients with EOPE and healthy pregnant controls (CTRL) were analyzed by RNA-seq. functions and mechanisms of circRNA_06354 in EOPE were investigated by a series of experiments. An EOPE rat model was constructed to detect the expression levels of circRNA_06354.

Results: The level of circRNA_06354 was altered in EOPE and CTRL individuals, as well as EOPE and CTRL rats. CircRNA_06354 had a sensitivity of 88.9% and a specificity of 100% in predicting EOPE. Subcellular localization indicated that circRNA_06354 was primarily detected in the cytoplasm of HTR8-/SV-neo cells and the cytotrophoblast of EOPE placentas. In addition, circRNA_06354 transcription was markedly higher than that of its linear counterpart. RNA pull-down assays implied that hsa-miR-92a-3p might sponge circRNA_06354. Vascular endothelial growth factor-A (VEGF-A) levels were found to be increased in EOPE patients. Moreover, overexpression of circRNA_06354 suppressed the migration, invasion and tube formation of trophoblastic cells invading spiral arteries or the endometrium.

Conclusion: CircRNA_06354 inhibits trophoblastic cell invasion, migration and tube formation toward the endometrium in the initiation of EOPE. The circRNA_06354/hsa-miR-92a-3p/VEGF-A axis might be a therapeutic target in the prevention and treatment of EOPE.