Gestational diabetes mellitus (GDM) causes both maternal and fetal adverse outcomes. The deregulation of microRNAs (miRNAs) in GDM suggests their involvement in GDM pathogenesis and complications. Exosomes are extracellular vesicles (EVs) of endosomal origin, released via exocytosis into the extracellular compartment. Through EVs, miRNAs are delivered in distant target cells and are able to affect gene expression. In this study, miRNA expression was analyzed to find new miRNAs that could improve GDM classification and molecular characterization. MiRNA were profiled in total plasma and EVs in GDM patients and normal glucose tolerance (NGT) women. Samples were collected at third trimester of gestation from two diabetes centers. MiRNA expression was profiled in a discovery cohort using the multiplexed NanoString nCounter Human v3 miRNA. Validation analysis was performed in a second independent cohort using RT-qPCR. A set of miRNAs resulted to be differentially expressed (DE) in total plasma and EVs in GDM. Among them, total plasma miR-222-3p and miR-409-3p were validated in the independent cohort. MiR-222-3p levels correlated with fasting plasma glucose (FPG) (p < 0.001) and birth weight (p = 0.012), whereas miR-409-3p expression correlated with FPG (p < 0.001) and inversely with gestational age (p = 0.001). The major validated target genes of the deregulated miRNAs were consistently linked to type 2 diabetes and GDM pathophysiology. MiR-222-3p and miR-409-3p are two circulating biomarkers that could improve GDM classification power and act in the context of the molecular events leading to the metabolic alterations observed in GDM.

Identification and validation of mir-222-3p and mir-409-3p as plasma biomarkers in gestational diabetes mellitus sharing validated target genes involved in metabolic homeostasis / Filardi, Tiziana; Catanzaro, Giuseppina; Emanuela Grieco, Giuseppina; Splendiani, Elena; Trocchianesi, Sofia; Santangelo, Carmela; Brunelli, Roberto; Guarino, Elisa; Sebastiani, Guido; Dotta, Francesco; Morano, Susanna; Ferretti, Elisabetta. - In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. - ISSN 1661-6596. - 23:8(2022), pp. 1-16. [10.3390/ijms23084276]

Identification and validation of mir-222-3p and mir-409-3p as plasma biomarkers in gestational diabetes mellitus sharing validated target genes involved in metabolic homeostasis

TIZIANA FILARDI;giuseppina catanzaro
;
ELENA SPLENDIANI;Sofia Trocchianesi;Roberto Brunelli;Francesco Dotta;Susanna Morano;Elisabetta Ferretti
2022

Abstract

Gestational diabetes mellitus (GDM) causes both maternal and fetal adverse outcomes. The deregulation of microRNAs (miRNAs) in GDM suggests their involvement in GDM pathogenesis and complications. Exosomes are extracellular vesicles (EVs) of endosomal origin, released via exocytosis into the extracellular compartment. Through EVs, miRNAs are delivered in distant target cells and are able to affect gene expression. In this study, miRNA expression was analyzed to find new miRNAs that could improve GDM classification and molecular characterization. MiRNA were profiled in total plasma and EVs in GDM patients and normal glucose tolerance (NGT) women. Samples were collected at third trimester of gestation from two diabetes centers. MiRNA expression was profiled in a discovery cohort using the multiplexed NanoString nCounter Human v3 miRNA. Validation analysis was performed in a second independent cohort using RT-qPCR. A set of miRNAs resulted to be differentially expressed (DE) in total plasma and EVs in GDM. Among them, total plasma miR-222-3p and miR-409-3p were validated in the independent cohort. MiR-222-3p levels correlated with fasting plasma glucose (FPG) (p < 0.001) and birth weight (p = 0.012), whereas miR-409-3p expression correlated with FPG (p < 0.001) and inversely with gestational age (p = 0.001). The major validated target genes of the deregulated miRNAs were consistently linked to type 2 diabetes and GDM pathophysiology. MiR-222-3p and miR-409-3p are two circulating biomarkers that could improve GDM classification power and act in the context of the molecular events leading to the metabolic alterations observed in GDM.
2022
gestational diabetes mellitus; gdm; mirna; mir-222-3p; mir-409-3p; extracellular
01 Pubblicazione su rivista::01a Articolo in rivista
Identification and validation of mir-222-3p and mir-409-3p as plasma biomarkers in gestational diabetes mellitus sharing validated target genes involved in metabolic homeostasis / Filardi, Tiziana; Catanzaro, Giuseppina; Emanuela Grieco, Giuseppina; Splendiani, Elena; Trocchianesi, Sofia; Santangelo, Carmela; Brunelli, Roberto; Guarino, Elisa; Sebastiani, Guido; Dotta, Francesco; Morano, Susanna; Ferretti, Elisabetta. - In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. - ISSN 1661-6596. - 23:8(2022), pp. 1-16. [10.3390/ijms23084276]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1633475
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