The miRNome of Depression
Abstract
:1. Introduction
2. miRNA Biogenesis, Function and Regulatory Properties
3. Studies Investigating Depression-Related miRNAs in the Brain
3.1. Brodmann Area 9 (BA9)
3.2. Brodmann Area 10 (BA10)
3.3. Brodmann Area 44 (BA44)
3.4. Anterior Cingulate Cortex (ACC)
3.5. Other Brain Regions
4. miRNA Studies of Depression and Antidepressant Treatments Investigating Blood and Body
4.1. Whole Blood
4.2. Serum/Plasma and Cerebrospinal Fluid (CSF)
4.3. Peripheral Blood Mononuclear Cells (PBMCs)
4.4. Extracellular Vesicles
- 1.
- Large extracellular vesicles (L-EVs), including apoptotic bodies, large oncosomes and microvesicles;
- 2.
- Small extracellular vesicles (S-EVs), including exosomes;
- 3.
- Extracellular particles (EPs), including exomeres and chromatimers.
4.5. Brain-Enriched miRNAs Found in Periphery
5. From Changes in the Brain to Changes in the Periphery: A Summary
5.1. miR-1202
5.2. miR-124-3p
5.3. miR-19a-3p
5.4. miR-135a-5p
5.5. miR-34 Family
6. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Ref. | Brain Region | miRNA | Regulation MDD vs. HC | Targeted Gene | Validation of Targeted Gene |
---|---|---|---|---|---|
[80] | Amygdala | miR-128-3p | Up | DVL1, LEF1, WNT5b | Direct—in vitro |
[75] | Lateral habenula | miR-320b-3p, miR-331-3p | Up | N/A | N/A |
miR-323a-3p | Up | ERBB4 | Direct—in vitro | ||
BA24 | miR-204-5p, miR-331-3p | Up | N/A | N/A | |
miR-323a-3p | Up | ERBB4 | Direct—in vitro | ||
[45] | BA9/BA46 | miR-484-5p, miR-26b-5p, miR-30d-5p, miR-197-3p | Down | N/A | N/A |
[74] | ACC | 117 miRNAs (4.16%) | Up | N/A | N/A |
54 miRNAs (2.13%) | Down | N/A | N/A | ||
[44] | BA9 | miR-30a-5p, miR-30e-5p | Up | ZDHHC21 | Direct—in vitro |
miR-200a-5p | Down | N/A | N/A | ||
[65] | BA44 | miR-124-3p | Down * | DDIT | Indirect |
[53] | BA10 | miR-19a-3p | Up | TNFa | N/A |
miR-20a-5p, miR-92a-1-3p | Down | N/A | N/A | ||
[85] | BA46 | miR-124-3p | Up | GRIA3, GRIA4, NR3C1 | Direct—in vitro |
[78] | Locus coeruleus | miR-17-5p, miR-20b-5p, miR-106a-5p, miR-330-3p, miR-541-3p, miR-582-5p, miR-890, miR-99-3p, miR-550-5p, miR-1179 | Up | RELN, GSK-3β, MAOA, CHRM1, PLCB1,GRIK1 | Indirect |
miR-409-5p, let-7g-3p, miR-1197 | Down | ||||
[64] | BA44 | miR-218-5p | Down | DCC | Direct—in vitro |
[86] | vPFC | miR-146a-5p, miR-146b-5p, miR-24-3p, miR-425-3p | Up | MAPK/Wnt pathway | Direct—in vitro |
[87] | Midbrain | miR-326 | Down | UCN1 | Direct—in vitro |
[77] | ACC | miR-184 and miR-34a-5p | Down | PDE4B, NCOA1, NCOR2 | Direct—in vitro |
[79] | BLA | miR-511, miR-340 | Up | GFRA1 | Direct—in vitro |
[63] | BA44 | miR-1202 | Down | GRM4 | Direct—in vitro |
[84] | Raphe nuclei | miR135a-5p | Down | SLC6A4, HTR1A | Direct—in vitro |
[58] | BA44 | miR-34c-5p, miR-139-5p, miR-195-5p, miR-320c-3p | Up | STAT1, SMOX | Indirect |
[52] | BA10 | miR-508-3p, miR-152-3p | Down | N/A | N/A |
[43] | BA9 | miR-142-5p, miR-137, miR-489, miR-148b, miR-101, miR-324-5p, miR-301a, miR-146a, miR-335, miR-494, miR-20b, miR-376a *, miR-190, miR-155, miR-660, miR-130a, miR-27a, miR-497, miR-10a, miR-20a, miR-142-3p | Down | DNMT3b, VEGFa, BCL-2 | Indirect |
[51] | BA10 | miR-185 *, 491-3p | Up | Trk2- T1 | Direct—in vitro |
Ref. | Tissue Source | miRNA | Regulation MDD vs. HC | Antidepressant Treatment | miRNA | Regulation by Treatment | Targeted Gene | Validation of Targeted Gene |
---|---|---|---|---|---|---|---|---|
[92] | Whole blood | miR-9-5p | Up | - | - | - | - | - |
[143] | BDEVs in blood | miR-17-5p | & | - | - | - | - | - |
[93] | BDEVs in blood | - | - | Escitalopram (8 weeks) | miR-30d-5p, miR-486-5p | Up # | NR3C1, SIRT1, SERPINE1, RPS6KB1, ATF6, PSEN1 | Indirect |
[150] | Plasma | miR-19b-3p, miR-3921 | Down | - | - | - | - | - |
miR-1180-3p | Up | - | - | - | - | - | ||
[142] | Serum exosomes | miR-139-5p | Up | - | - | - | - | - |
[62] | Blood exosomes | miR-139-5p | Up | - | - | - | MAP2 | Direct—in vitro |
[151] | Buffy coat | - | - | Venlafaxine (12 weeks) | miR-135a-5p | X | - | - |
[152] | Whole blood | miR-34b-5p, miR-34c-5p | C * | - | - | - | - | - |
[117] | Plasma | miR-134 | Down | Personalized (8 weeks) | miR-134 | Up | - | - |
[102] | Whole blood | - | - | Escitalopram (2 weeks) | 33 miRNAs | Up | - | - |
12 miRNAs | Down | - | - | |||||
[153] | Serum | miR-221-3p | Up | - | - | - | IRF2 | Direct—in vitro |
[103] | Whole blood | pmiR-chr11 | Up | - | - | - | BRPF1 | Direct—in vitro |
miR-1275 | Down | - | - | - | - | - | ||
[115] | Plasma | miR-184 | Down | - | - | - | - | - |
[116] | Plasma | let-7g-5p, miR-103a-3p, miR-107, and miR-142-3p | Down | - | - | - | - | - |
[126] | PBMC/Monocytes | let-7e-5p, miR-21-5p, miR-146a, miR-155, miR-146a, miR-155 | Down | Personalized (4 weeks) | let-7e-5p, miR-223, miR-146a, miR-155, miR-21-5p, miR-14 | Up | TLR4 | Indirect |
[154] | Plasma | - | - | Duloxetine (6–8 weeks) | miR-23a-3p, miR-16-5p, miR-146a-5p, miR-21-5p | 10th percentile | - | - |
[101] | Whole blood | - | - | Duloxetine (8 weeks) | miR-3688, miR-5695 | Up # | - | - |
[114] | Serum | miR-16-5p, miR-135a-5p, miR-1202 | Down | - | - | - | - | - |
[155] | Whole blood | miR-132-3p | Up | - | - | - | - | - |
[156] | Whole blood | miR-132-3p, miR-135b, miR-181b | Up | - | - | - | - | - |
miR-155 | Up | - | - | - | SIRT1 | Direct—in vitro | ||
[53] | PBMC | miR-19a-3p | Up | - | - | - | TNFa | Indirect |
[111] | Serum | miRNA-34a-5p, miRNA-221-3p | Up | Paroxetine (8 weeks) | miRNA-34a-5p, miRNA-221-3p | Down | - | - |
miRNA-451a | Down | miRNA-451a | Up | - | - | |||
[105] | Plasma | miR-132-3p, miR-124-3p | Up | Citalopram (8 weeks) | miR-124-3p | Up | - | - |
miR-132 | Down | - | - | |||||
[100] | Serum | - | - | SSRI/SNRI (4 weeks) | miR-183, miR-212 | Up | - | - |
SSRI (4 weeks) | miR-16-5p | Up | - | - | ||||
[97] | Whole blood | miR-1202 | Down # | Duloxetine (8 weeks) | miR-1202 | Up # | - | - |
[85] | Serum | miR-124-3p | Up | - | - | - | - | - |
[86] | Whole blood/ Plasma | - | - | Personalized (8 weeks) | miR-146a-5p, miR-146b-5p, miR-24-3p, miR-425-3p, miR-3074-5p | Down # | MAPK/Wnt | Direct—in vitro |
[141] | Serum exosomes | miR-1255a, miR-3161, miR-99a-3p, miR-205-5p, miR-26a-1-3p, miR-139-5p, miR-7849-3p, miR-195-5p, miR-125b-2-3p, miR-664a-3p, let-7c-5p, miR-197-3p | Up | - | - | - | - | - |
miR-499a-5p, miR-4732-3p, miR-222-5p, miR-1291, miR-668-3p, miR-425-3p, miR-6511a-3p, iR-145-3p, miR-200a-3p, miR-143-3p, miR-196b-5p, miR-99a-5p, miR-144-3p, miR-584-5p, miR-210-3p, miR-183-5p, miR-107, miR-130b-5p, miR-589-5p, miR-1910-5p | Down | - | - | - | - | - | ||
[96] | Whole blood | - | - | Desvenlafaxine (8 weeks) | miR-1202 | Up | - | - |
[157] | Whole blood | miR-15a-5p | Up | - | - | - | FKBP5 | Direct—in vitro |
[130] | PBMC | miR-34b-5p, miR-34c-5p | Up | - | - | - | Notch1 | Indirect |
[158] | Whole blood | miR-199a-5p, miR-345-5p, miR-330-3p, miR-425-3p, miR-24-3p, miR-29c-5p | Up | - | - | - | - | - |
let-7a-5p, let-7f-5p, let-7d-5p, miR-1915-3p | Down | |||||||
[129] | PBMC | miR-124-3p | Up | Personalized (8 weeks) | miR-124-3p | Down | - | - |
[159] | Whole blood | let-7b, let-7c | Down | - | - | - | - | - |
[128] | PBMC | miR-29c | Up * | - | - | - | - | - |
[160] | Whole blood | miR-132-3p | Up | - | - | - | - | - |
[148] | Plasma | - | - | Escitalopram (12 weeks) | 23 miRNAs | Up | - | - |
17 miRNAs | Down | - | - | |||||
[161] | Plasma | miR-451a, miR-17-5p, miR-223-3p | Up | - | - | - | - | - |
miR-320a | Down | |||||||
[109] | CSF | miR-16-5p | Down | - | - | - | SLC6A4 | Direct—in vitro |
Serum | miR-16-5p | Down | - | - | - | |||
[110] | CSF | miR-34a-5p, miR-221-3p, let-7d-3p | Up | - | - | - | - | - |
miR-451a | Down | |||||||
Serum | miR-125a-5p, miR-30a-5p, let-7d-3p, miR-34a-5p, miR-221-3p, miR-29b-3p, miR-10a-5p, miR-375 | Up | ||||||
miR-155-5p, miR-33a-5p, miR-139-5p, miR-590-5, miR-185-5p, miR-106b-5p, miR-15b-5p, miR-451a | Down | |||||||
[149] | Whole blood | miR-132 | Up | - | - | - | - | - |
[107] | Plasma | miR-144-5p | Down | Personalized (8 weeks) | miR-144-5p | Up | - | - |
[95] | Whole blood | miR-335 | Down | Citalopram (4 weeks) | miR-335 | Up | GRM4 | Direct—in vitro |
miR-583, mir-650, miR-708, miR-654 | Down | |||||||
miR-644, miR-450b, mir-328, miR-182 | Up | |||||||
[125] | PBMC | miRNA-26b, miRNA-1972, miRNA-4485, miRNA-4498, miRNA-4743 | Up | - | - | - | - | - |
[84] | Whole blood | miR-135a-5p | Down | CBT (3 weeks) | miR-135a-5p | Up | SLC6A4, HTR1A | Direct—in vitro |
[63] | Whole blood | miR-1202 | Down | Citalopram (8 weeks) | miR-1202 | Up | GRM4 | Direct—in vitro |
[104] | Serum | miR-182, miR-132 | Up | - | - | - | BDNF | Direct—in vitro |
[94] | Whole blood | - | - | Escitalopram (12 weeks) | 28 miRNAs | Up | - | |
miR-34c-5p, miR-770-5p | Down | |||||||
[124] | PBMC | miR-589, miR-579, miR-941, miR-133a, miR-494, miR-107, miR-148a, miR-652, miR-425-3p | Up | Personalized (8 weeks) | miR-20b-3p, miR-433, miR-409-3p, miR-410, miR-485-3p, miR-133a, miR-145 | Up | - | - |
miR-517b, miR-636, miR-1243, miR-381, miR-200c | Down | miR-331-5p | Down |
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Żurawek, D.; Turecki, G. The miRNome of Depression. Int. J. Mol. Sci. 2021, 22, 11312. https://doi.org/10.3390/ijms222111312
Żurawek D, Turecki G. The miRNome of Depression. International Journal of Molecular Sciences. 2021; 22(21):11312. https://doi.org/10.3390/ijms222111312
Chicago/Turabian StyleŻurawek, Dariusz, and Gustavo Turecki. 2021. "The miRNome of Depression" International Journal of Molecular Sciences 22, no. 21: 11312. https://doi.org/10.3390/ijms222111312