ArticleAmerican journal of translational research2024
Hypoxia-induced upregulation of hsa-miR-584-3p suppresses endometrial glandular epithelial cell function by targeting DKK-1.
Article in American journal of translational research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
objectiveTo 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.
methodsEECs 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.
resultsHypoxic 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.
conclusionHypoxia-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.
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