Short communication: Upregulation of hypoxia/reoxygenation-induced Shc3 by downregulated miR-455-5p, suppresses trophoblasts implantation and is associated with placental inflammation and angiogenesis of preeclampsia

Preeclampsia is characterized by insufficient implantation of trophoblasts. It is relevant in the failure adaptation of trophoblasts to changes in the intrauterine embryo development environment. Fewer miRNAs have been reported on this. MiR-455-5p expressed lowly in preeclampsia but its role remains unknown. Combining cell and molecular biology methods, we suggested the function and relevant mechanisms of miR-455-5p and its potential target Shc3 in preeclampsia. In vitro, HTR-8/SVneo migrated and invaded more rapidly under H/R than in hypoxic or normoxic conditions when miR-455-5p was overexpressed. And the apoptosis of HTR-8/SVneo is in contrast to the migration and invasion in H/R. Shc3 was identified as a direct downstream target gene of miR-455-5p, where overexpression of this gene reversed the miR-455-5p impact, promoting apoptosis and suppressed invasion and migration of HTR-8/SVneo under H/R. Shc3 was highly expressed in H/R, but its level was low in isolated hypoxic or normoxic environments. Further, Shc3 overexpression is involved in placental inflammation and angiogenesis inhibition. Finally, we got the conclusion that the downregulation of miR-455-5p in preeclampsia contributes to the elevation of Shc3 in trophoblast, thereby deteriorating trophoblast cells implantation. The elevated Shc3 is associated with placental inflammation and angiogenesis inhibition. Shc3 serves as a potential biomarker for preeclampsia diagnosis and treatment. Overall design: To explore the target genes of miR-455-5p that affect the phenotypes of migration, invasion, and apoptosis of HTR8/Svneo cells under hypoxia/reoxygenation conditions, we overexpressed miR-455-5p mimic and miR-455-5p mimic-NC in HTR8/Svneo under hypoxia/reoxygenation. We detected the transcriptomic gene changes in HTR8/Svneo by RNA-Seq.