%0 Journal Article
%T Hypoxia-induced upregulation of hsa-miR-584-3p suppresses endometrial glandular epithelial cell function by targeting DKK-1.
%A Zhang W
%A Wang H
%A Deng C
%J Am J Transl Res
%V 16
%N 5
%D 2024
%M 38883346
%F 3.94
%R 10.62347/PFCF4169
%X <B>OBJECTIVE: </B>To investigate the impact of hypoxia on microRNA (miRNA) expression profiles in endometrial glandular epithelial cells (EECs) and elucidate potential mechanisms underlying proliferation, migration, and invasion.<BR><B>METHODS: </B>EECs in the logarithmic growth phase were exposed to normoxic (21% oxygen) and hypoxic (1% oxygen) conditions. MiRNA expression profiles were analyzed using RNA sequencing, and differential expression of hsa-miR-584-3p was confirmed by real-time quantitative PCR (RT-qPCR). Target prediction through TargetScan identified Dickkopf-1 (DKK-1) as a target gene of hsa-miR-584-3p. The interaction between hsa-miR-584-3p and DKK-1 was validated through a double-luciferase reporter gene assay and Western blotting. Cell proliferation, migration, and invasion were assessed using the Cell Counting Kit-8 (CCK-8) assay, wound healing assay, and Transwell invasion assay, respectively.<BR><B>RESULTS: </B>Hypoxic conditions significantly upregulated the expression of hsa-miR-584-3p in EECs (P<0.001). TargetScan analysis predicted DKK-1 as a downstream target of hsa-miR-584-3p. The double-luciferase reporter gene assay confirmed the binding of hsa-miR-584-3p to the 3' untranslated region of the DKK-1 gene, leading to reduced DKK-1 protein expression (P<0.001). Functional assays demonstrated decreased proliferation and increased migration and invasion of EECs under hypoxia.<BR><B>CONCLUSIONS: </B>Hypoxia-induced upregulation of hsa-miR-584-3p suppresses the function of EECs by targeting DKK-1 protein activity, thereby influencing their proliferation, migration, and invasion.