Table 3.
Functional roles and validated targets of interesting exomiRNA identified between group comparisons
| Group Comparison | Identified Exosomal miRNAs | Function | Validated Targets/Pathways | References | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| miRNA | Mean (Log2) | log FC | |||||||||
| LOPE | EOPE | N (≤33 weeks) | N (≥34 weeks) | EOPE vs N (≤33 weeks) | LOPE vs N (≥34 weeks) | ||||||
| EOPE/N (≤33 weeks) vs LOPE/N (≥34 weeks) | |||||||||||
| hsa-miR-504-5p | 2,09 | 3,01 | 2 | 3,3 | 1,01 | -1,21 | Cell Proliferation and Invasion | Targets LOXL2 in cancer | 44 | ||
| hsa-miR-2113 | 3,76 | 3,01 | 4,7 | 4,88 | -1,69 | -1,12 | ND | ND | |||
| hsa-miR-374c-5p | 2,09 | 2,2 | 3,9 | 3,3 | -1,7 | -1,21 | Inflammation | Regulates MID1 protein expression | 45 | ||
| LOPE | EOPE | N (≤33 weeks) | EOPE vs N (≤33 weeks) | EOPE vs LOPE | |||||||
| EOPE/N (≤33 weeks) vs EOPE/LOPE | hsa-miR-204-5p | 3,57 | 2,52 | 4,08 | -1,56 | -1,05 | Epithelial-to-Mesenchymal Transition | Repression of TGF-β2–induced Epithelial-to-Mesenchymal Transition in the presence of SMAD4 small interfering RNA. | 46 | ||
| hsa-miR-139-5p | 3,85 | 2,79 | 4,8 | -2,02 | -1,07 | Cell proliferation and apoptosis | Regulates cell proliferation an apoptosis by targeting the Brg1 gene | 47 | |||
| hsa-miR-449c-5p | 4,46 | 3,37 | 4,95 | -1,58 | -1,09 | Multiciliogenesis | Targets the cell cycle and notch pathway via DLL1 and NOTCH1 | 48 | |||
| hsa-miR-1275 | 4,29 | 3,01 | 4,52 | -1,51 | -1,28 | cell migration, invasion and proliferation | Targets IGF-1R and CCR7 in tumor progression | 49 | |||
| hsa-miR-320d | 4,81 | 3,37 | 4,39 | -1,02 | -1,44 | Apoptosis | Regulates apoptosis by targeting TRIAP1 and NET1 | 50 | |||
| hsa-miR-452-5p | 3,67 | 1,79 | 3,58 | -1,8 | -1,89 | Cell proliferation and Migration | Targets the CPEB3/EGFR axis in tumor progression | 51 | |||
| hsa-miR-378b | 3,76 | 1,2 | 3,17 | -1,97 | -2,56 | Angiogenesis | Promotes angiogenesis by targeting Suppressor of fused (SuFu) and Fus-1 expression | 52 | |||
| LOPE | EOPE | N (≥34 weeks) | LOPE vs N (≥34 weeks) | EOPE vs LOPE | |||||||
| LOPE/N (≥34 weeks) vs EOPE/LOPE | hsa-miR-451a | 12,75 | 10,15 | 11,1 | 1,68 | -2,6 | Cell Survival | Inhibition of cell survival by targeting calcium-binding protein 39 (CAB39, also known as MO25a) to inhibit the key AMPK kinase LKB1 (liver kinase B1), causing AMPK inactivation | 53 | ||
| hsa-miR-379-5p | 3,93 | 2,79 | 2,71 | 1,22 | -1,15 | Glucose Secretion | Suppresses glucose induced insulin secretion by targeting Myotrophin (Mtpn) | 54 | |||
| hsa-miR-26a-5p | 3,67 | 4,72 | 4,71 | -1,04 | 1,05 | Angiogenesis | targets VEGF-A expression through PIK3C2α | 55 | |||
| hsa-miR-376b-3p | 2,35 | 3,37 | 3,93 | -1,58 | 1,02 | Autophagy | Regulates autophagy by targeting ATG4C and BECN1 (Beclin 1) | 56 | |||
| hsa-miR-150-5p | 3,35 | 4,45 | 4,93 | -1,58 | 1,1 | Cell Proliferation and Migration | HIF-1α expression | 57 | |||
| hsa-miR-517c-3p | 3,67 | 4,72 | 4,77 | -1,1 | 1,05 | Trophoblast invasion | Overexpression decreases invasion through the dysregulation of TNFSF15 expression and sFLT1 | 58 | |||
| EOPE/N (≤33 weeks) vs LOPE/N (≥34 weeks) vs EOPE/LOPE | LOPE | EOPE | N (≤33 weeks) | N (≥34 weeks) | EOPE vs N (≤33 weeks) | LOPE vs N (≥34 weeks) | EOPE vs LOPE | ||||
| hsa-miR-122-5p | 0,76 | 5,72 | 0,2 | 4,65 | 5,72 | -3,88 | 4,96 | Cholesterol Metabolism | Targets CAT1 | 59 | |
| hsa-miR-3605-3p | 4,16 | 3,01 | 4,32 | 3,13 | -1,31 | 1,03 | -1,15 | ND | ND | ||
Note: All fold changes associated with the complement analyses are represented in Log2 scale (LogFC), statistically, significant exomiRNAs were selected based on an arbitrary |FC| ≥1.4 and FDR ≤0.05. Mean expression values are presented in Log2 scale.
Abbreviations: ND, not detected; N, normotensive pregnancies; EOPE, early onset preeclampsia; LOPE, late onset preeclampsia; FC, fold change.