Study on the regulation of trophoblast activity by abnormally expressed hsa_circ_0024838/miR-543/HIF1A in patients with gestational diabetes mellitus

Qian Liu; Juan Gui; Lianzhi Wu

doi:10.1016/j.placenta.2024.04.006

Study on the regulation of trophoblast activity by abnormally expressed hsa_circ_0024838/miR-543/HIF1A in patients with gestational diabetes mellitus

Placenta. 2024 Apr 18:151:27-36. doi: 10.1016/j.placenta.2024.04.006. Online ahead of print.

Authors

Qian Liu¹, Juan Gui¹, Lianzhi Wu²

Affiliations

¹ Center for Reproductive Medicine, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
² Department of Obstetrics, Renmin Hospital of Wuhan University, Wuhan, 430060, China. Electronic address: wulianzhi1983@163.com.

PMID: 38701658
DOI: 10.1016/j.placenta.2024.04.006

Abstract

Introduction: This study aimed to screen circRNAs involved in gestational diabetes mellitus (GDM)-related macrosomia. One differentially expressed circRNA (DEC), hsa_circ_0024838, was further tested for its potential role and mechanism in trophoblasts.

Methods: DECs in GDM were selected through GSE182737 and GSE194119. The targets were predicted for DECs and microRNAs (miRNAs), to complete the construction of the circRNA-miRNA-gene network. Functional annotation and related biological pathway enrichment analysis were performed on the target genes of miRNAs in the network. Subsequently, the expression levels of hsa_circ_0024838, miR-543, and HIF1A mRNA were identified by real-time quantitative real-time PCR (RT-qPCR) in GDM patients. Trophoblast activity was assessed via CCK-8 assay, apoptosis assay, and Matrigel invasion assay. Finally, interactions between miR-543 and either hsa_circ_0024838 or HIF1A were confirmed using dual-luciferase reporter assays.

Results: A GDM-related circRNA-miRNA-genes interaction network was constructed, consisting of 35 circRNAs, 46 miRNAs, and 122 target genes. Functional enrichment revealed that the enriched pathways were involved in GDM. Hsa_circ_0024838 and HIF1A mRNA expression levels were upregulated in GDM, while miR-543 expression levels were downregulated. A significant positive correlation between hsa_circ_0024838 and newborn weight was observed. Both hsa_circ_0024838 and HIF1A possessed binding sites for miR-543. Overexpressing hsa_circ_0024838 in high-glucose (HG)-cultured trophoblasts can partially reverse HG-induced reduction in trophoblast cell proliferation/migration and increase apoptosis. But this reversal can be negated by co-transfection with miR-543 mimics. The effects of miR-543 can be counteracted by HIF1A.

Discussion: Hsa_circ_0024838 can regulate the expression of HIF1A by interacting with miR-543. This regulates the HIF1A signaling pathway and enhance vitality in trophoblast cells.

Keywords: Gestational diabetes mellitus; HIF1A; Hsa_circ_0024838; Trophoblast.