Table 2. Altered maternal circulating miRNAs of placental origin and their known targets and functional outcomes in pregnancies complicated by maternal diabetes.
| Diabetes type | miRNA Regulation | Source | Target | Functional outcome | Reference |
|---|---|---|---|---|---|
| GDM | ↑ miR-135a-5p | Maternal plasma EVs (including characterisation of placenta-derived EVs based on PLAP expression) | ↑ SIRT1 | ↑ trophoblast proliferation, invasion and migration | [273] |
| GDM | ↑ miR-130b-3p | Secreted EVs from cultured placental MSCs | ↓ ICAM-1 | ↑ HUVEC proliferation, migration and angiogenesis | [274] |
| GDM | ↓ miR-140-3p ↓ miR-574-3p |
Secreted EVs from cultured placental villous explants | ↓ VEGF | ↑ cell proliferation, migration and tube formation | [275] |
| GDM | ↑ miR-125a-3p ↑ miR-224-5p ↑ miR-584-5p ↑ miR-186-5p ↑ miR-22-3p ↑ miR-99b-5p ↑ miR-433-3p ↑ miR-197-3p ↑ miR423-3p ↓ miR-208a-3p ↓ miR-335-5p ↓ miR-451a ↓ miR-145-3p ↓ miR-369-3p ↓ miR-483-3p ↓ miR-203a-3b ↓ miR-574-3p ↓ miR-144-3p ↓ miR-6795-5p ↓ miR-550a-3-3p ↓ miR-411-5p ↓ miR-550a-3-3p ↓ miR-140-3p |
Secreted EVs from cultured placental villous explants | – | ↓ primary skeletal muscle cell insulin-stimulated migration and glucose uptake | [276] |
| GDM | ↓ miR-516-5p ↓ miR-517-3p ↓ miR-518-5p ↓ miR-222-3p ↓ miR-16-5p |
Maternal urine EVs (including characterisation of placenta-derived EVs based on PLAP expression) | IRS4 GALNT RECK ALG3 AKT3 TIMP3 KIT L2HGDH KI2FC RAP1 HOXC8 PD-L1 |
Altered insulin signalling, metabolic homeostasis and inflammatory response | [199] |
| GDM | ↑ miR-520h ↑ miR-1323 ↑ miR-136-5p ↑ miR-342-3p |
Maternal serum EVs (including characterisation of placenta-derived EVs based on PLAP expression) | ↓ AMPK ↓ GLUT2 |
Altered β-cell insulin secretion, β-oxidation and glucose transport | [200] |
| T1DM | No studies identified. | ||||
| T2DM | No studies identified. | ||||
Abbreviations: AKT, RAC-gamma serine/threonine-protein kinasel ALG3, asparagine-linked glycosylation protein 3 homolog; AMPK, adenosine monophosphate-activated protein kinase; GALNT, polypeptide N-acetylgalactoaminyltransferase; GLUT, glucose transporter; HOX, homeobox; HUVEC, human umbilical vein endothelial cell; ICAM, intracellular adhesion molecule; IRS, insulin receptor substrate; KI2FC, kinesin family member 2C; KIT, KIT proto-oncogene, receptor tyrosine kinase; L2HGDH, L-2-hydroxyglutarate dehydrogenase; MSC, mesenchymal stem cell; PD-L, programmed death-ligand; PLAP, placental alkaline phosphatase; RAP, Ras-related protein; RECK, reversion inducing cysteine rich protein with kazal motifs; SIRT, Sirtuin; TIMP3, tissue inhibitor of metalloproteinase-3; VEGF, vascular endothelial growth factor.