MicroRNA-125b regulates vitamin D resistance by targeting CYP24A1 in the progression of gestational diabetes mellitus

Vitamin D deficiency is prevalent in pregnancy and has been associated with increased occurrences of preeclampsia, cesarean delivery, neonatal bacterial vaginosis, and gestational diabetes. CYP24A1, recognized as a key factor in vitamin D metabolism homeostasis, encodes 24-hydroxylase responsible fo...

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Published in:The Journal of steroid biochemistry and molecular biology 2024-05, Vol.239, p.106475, Article 106475
Main Authors: Milan, K.L., Jayasuriya, Ravichandran, Harithpriya, Kannan, Anuradha, M., Ramkumar, Kunka Mohanram
Format: Article
Language:English
Subjects:
CYP24A1
Diabetes, Gestational - genetics
Diabetes, Gestational - metabolism
EGDM
Female
GDM
Humans
Infant, Newborn
MicroRNAs - genetics
MiR-125b-5p
Pregnancy
Receptors, Calcitriol - genetics
Receptors, Calcitriol - metabolism
Vitamin D
Vitamin D3 24-Hydroxylase - genetics
Vitamin D3 24-Hydroxylase - metabolism
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Summary:Vitamin D deficiency is prevalent in pregnancy and has been associated with increased occurrences of preeclampsia, cesarean delivery, neonatal bacterial vaginosis, and gestational diabetes. CYP24A1, recognized as a key factor in vitamin D metabolism homeostasis, encodes 24-hydroxylase responsible for converting 25(OH)D3 and 1,25(OH)2D3 into inactive metabolites. Recently, we have reported CYP24A1 overexpression in patients with gestational diabetes mellitus (GDM) and trophoblast cells exposed to hyperglycemia. In this study, we explored miRNA-mediated regulation of CYP24A1 in GDM progression, validating our findings through silencing experiments in a trophoblast cell line. In silico tools identified miR-125b-5p as a putative target of CYP24A1. Expression analysis revealed downregulation of miR-125b-5p in blood samples from early GDM and GDM compared to healthy pregnant women, positively correlating with vitamin D levels. Hyperglycemic exposure in human trophoblastic cell lines (BeWo) decreased miR-125b-5p expression, concomitant with an increase in CYP24A1. To confirm the regulatory role of miR-125b on CYP24A1, we transfected BeWo cells with antimiR-125b or miR-125b mimic. AntimiR-125b transfection heightened CYP24A1 levels, while miR-125b mimic overexpression resulted in decreased CYP24A1 expression. These findings establish miR-125b as a regulator of CYP24A1. To explore the influence of miR-125b on vitamin D metabolism, trophoblast cells overexpressing miR-125b were treated with 0.1 and 1 µM calcitriol. Hyperglycemic conditions exhibited a reduction in CYP24A1 levels. Collectively, our results indicate that miR-125b may regulate vitamin D metabolism by targeting CYP24A1, contributing to GDM progression. These findings may pave the way for understanding vitamin D resistance in concurrent GDM development and identifying novel miRNAs targeting CYP24A1. •Overexpression of CYP24A1 in gestational diabetes mellitus (GDM) patients and hyperglycemia-exposed trophoblast cells.•miR-125b-5p downregulation was observed in blood samples from early GDM and GDM patients compared to healthy pregnant women.•Hyperglycemic exposure in trophoblast cells results in decreased miR-125b-5p expression and increased CYP24A1 expression.•Transfection experiments confirm the regulatory role miR-125b on CYP24A1 expression.•Cells overexpressing miR-125b-5p shows reduction in CYP24A1 levels under hyperglycemic condition.
ISSN:0960-0760
1879-1220
1879-1220
DOI:10.1016/j.jsbmb.2024.106475