Bioinformatic Analysis of Autism-Related miRNAs and Their PoTential as Biomarkers for Autism Epigenetic Inheritance
Abstract
:1. Introduction
2. Materials and Methods
2.1. Compilation of Autism-Related miRNAs
2.2. Identification of miRNAs Expressed in Peripheral Blood Mononuclear Cells (PBMCs), Sperm, and Neurons
2.3. Analysis of Genes Targeted by the Autism-Related miRNAs
2.4. Pathway Enrichment Analysis
2.4.1. Metascape
2.4.2. gProfiler
2.5. miRNAs Enrichment Analysis
3. Results
3.1. Autism-Related miRNAs: miRNA-to-Gene Analysis
3.2. miRNAs Expressed in PBMCs, Neurons, and Sperm
3.3. Identification of Genes Targeted by Candidate Autism-Related miRNA
3.4. Enrichment Analysis of All the Genes Targeted by the 18 Candidate Autism-Related miRNAs
3.5. Enrichment Analysis of Target Genes Common to Neurons and Sperm
3.6. Enrichment Analysis of Target Genes Common to PBMCs, Neurons, and Sperm
3.7. Autism-Related miRNAs: Gene-to-miRNA Analysis (miRNA Enrichment)
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
ADHD | Attention deficit hyperactivity disorder |
ASD | Autism spectrum disorder |
E | Enrichment value |
eQTL | Expression quantitative trait loci |
FDR | False discovery rate |
GO | Gene Ontology |
GWAS | Genome wide association studies |
miRNA | microRNA |
Padj | Ajusted p-value |
PBMC | Peripheral blood mononuclear cells |
PCR | Polymerase chain reaction |
RPM | Reads per million |
SFARI | Simons Foundation Autism Research Initiative |
sncRNA | small non-coding RNA |
SNP | Single nucleotide polymorphisms |
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Enrichment Analysis | Biological Pathways Enrichment Map | Human Phenotypes Ontology Enrichment Map |
---|---|---|
| OC = 0.5 | JC = 0.3 |
| OC = 0.5 | OC = 0.5 |
| OC = 0.5 | OC = 0.5 |
Sperm | Neurons | PBMCs |
---|---|---|
hsa-miR-424-5p | hsa-miR-432-5p | hsa-miR-451a |
hsa-miR-619-5p | hsa-miR-196a-5p | hsa-miR-320a-3p |
hsa-miR-193b-3p | hsa-miR-494-3p | hsa-miR-144-3p |
hsa-miR-664a-3p |
Sperm and Neurons | Sperm and PBMCs | Neurons and PBMCs |
---|---|---|
hsa-miR-106a-5p | hsa-miR-223-3p | hsa-miR-874-3p |
hsa-miR-379-5p | hsa-miR-142-3p | hsa-miR-199a-5p |
hsa-miR-148a-5p | hsa-miR-142-5p | |
hsa-miR-146a-5p | ||
hsa-miR-15a-5p | ||
hsa-miR-29a-3p | ||
hsa-miR-29b-3p | ||
hsa- miR-29c-3p, | ||
hsa-miR-19a-3p | ||
hsa-miR-155-5p |
miRNA | |
---|---|
hsa-miR-106a-5p | hsa-miR-7-5p |
hsa-miR-223-3p | hsa-let-7a-5p |
hsa-miR-142-3p | hsa-miR-128-3p |
hsa-miR-146a-5p | hsa-miR-99a-5p |
hsa-miR-155-5p | hsa-miR-15b-5p |
hsa-miR-15a-5p | hsa-miR-484 |
hsa-miR-29b-3p | hsa-miR-19b-3p |
hsa-miR-29c-3p | hsa-miR-106b-5p |
hsa-miR-19a-3p | hsa-miR-221-3p |
hsa-miR-29a-3p | hsa-miR-574-3p |
hsa-miR-424-5p | hsa-miR-93-5p |
hsa-miR-619-5p | hsa-miR-27a-3p |
hsa-miR-143-3p | hsa-miR-335-3p |
hsa-miR-140-5p | hsa-miR-130a-3p |
hsa-miR-23a-3p | hsa-miR-146b-5p |
miRNA | References |
---|---|
hsa-let-7a-5p | [25] (blood); [68] (brain); [69] (saliva) |
hsa-miR-93-5p | [70] (cerebellar cortex); [27] (monocytes); [71] (serum) |
hsa-miR-27a-3p | [70] (cerebellar cortex); [72] (serum); [73] (saliva); [74] (blood) |
hsa-miR-146b-5p | [70] (cerebellar cortex); [75] (saliva); [76] (brain) |
hsa-miR-140-5p | [70] (cerebellar cortex); [76] (brain); [77] (saliva) |
hsa-miR-23a-3p | [70] (cerebellar cortex); [73] (saliva); [78] (brain); [79] (saliva); [80] (brain); [81] (serum) |
hsa-miR-7-5p | [70] (cerebellar cortex); [68] (brain); [73] (saliva); [71] (serum); [79] (saliva); [82] (plasma) |
hsa-miR-15b-5p | [70] (cerebellar cortex); [25] (blood); [83] (blood) |
hsa-miR-484 | [70] (cerebellar cortex); [78] (brain); [84] (plasma) |
hsa-miR-19b-3p | [72] (serum); [25] (blood); [68] (brain); [85] (serum) |
hsa-miR-106b-5p | [70] (cerebellar cortex); [72] (serum); [86] (serum); [87] (serum); [82] (plasma) |
hsa-miR-221-3p | [78] (brain); [80] (brain); [82] (plasma) |
hsa-miR-574-3p | [25] (blood); [71] (serum); [76] (brain) |
hsa-miR-130a-3p | [72] (serum); [76] (brain) |
hsa-miR-335-3p | [73] (saliva); [78] (brain) |
hsa-miR-143-3p | [80] (brain); [77] (saliva) |
hsa-miR-128-3p | [70] (cerebellar cortex); [88] (serum) |
hsa-miR-99a-5p | [80] (brain); [82] (plasma) |
miRNA | Total | Sperm and Neurons | Sperm, Neurons, and PBMCs | Target Genes Related to Autism | ||
---|---|---|---|---|---|---|
Total | Sperm and Neurons | Sperm, Neurons, and PBMCs | ||||
hsa-miR-335-3p | 2549 | 822 | 488 | 292 | 120 | 54 |
hsa-miR-93-5p | 2017 | 754 | 476 | 227 | 110 | 57 |
hsa-miR-106b-5p | 2002 | 720 | 456 | 211 | 97 | 49 |
hsa-miR-15b-5p | 1898 | 715 | 451 | 219 | 100 | 59 |
hsa-miR-484 | 1861 | 749 | 534 | 196 | 102 | 72 |
hsa-miR-27a-3p | 1827 | 655 | 390 | 210 | 102 | 52 |
hsa-miR-128-3p | 1807 | 636 | 379 | 201 | 104 | 52 |
hsa-miR-23a-3p | 1726 | 574 | 359 | 191 | 92 | 48 |
hsa-miR-7-5p | 1694 | 623 | 393 | 186 | 96 | 54 |
hsa-miR-19b-3p | 1675 | 630 | 392 | 243 | 125 | 61 |
hsa-let-7a-5p | 1585 | 539 | 338 | 152 | 75 | 37 |
hsa-miR-143-3p | 1478 | 557 | 334 | 185 | 97 | 49 |
hsa-miR-221-3p | 1443 | 559 | 373 | 186 | 92 | 53 |
hsa-miR-130a-3p | 1351 | 501 | 316 | 169 | 73 | 39 |
hsa-miR-146b-5p | 1331 | 489 | 299 | 161 | 80 | 39 |
hsa-miR-140-5p | 1229 | 487 | 308 | 181 | 99 | 50 |
hsa-miR-99a-5p | 1037 | 405 | 263 | 103 | 60 | 30 |
hsa-miR-574-3p | 954 | 345 | 213 | 100 | 49 | 23 |
miRNA | Metascape | gProfiler and EnrichmentMap |
---|---|---|
hsa-miR-335-3p | 2 | 5 |
hsa-miR-93-5p | 1 | 3 |
hsa-miR-106b-5p | 3 | 3 |
hsa-miR-15b-5p | 3 | 4 |
hsa-miR-484 | 1 | 1 |
hsa-miR-27a-3p | 2 | 3 |
hsa-miR-128-3p | 3 | 3 |
hsa-miR-23a-3p | 0 | 3 |
hsa-miR-7-5p | 2 | 4 |
hsa-miR-19b-3p | 1 | 2 |
hsa-let-7a-5p | 1 | 1 |
hsa-miR-143-3p | 2 | 2 |
hsa-miR-221-3p | 3 | 1 |
hsa-miR-130a-3p | 2 | 2 |
hsa-miR-146b-5p | 5 | 4 |
hsa-miR-140-5p | 3 | 4 |
hsa-miR-99a-5p | 0 | 0 |
hsa-miR-574-3p | 0 | 1 |
miRNA | FDR | Enrichment |
---|---|---|
has-miR-19b-3p | 4.96 × 10−8 | 0.97 |
has-miR-15b-5p | 0.00035 | 0.727 |
hsa-miR-21-5p | 0.000353 | 0.787 |
hsa-miR-16-5p | 0.00724 | 0.447 |
hsa-miR-744-5p | 0.0126 | 0.77 |
hsa-miR-181a-5p | 0.0149 | 0.678 |
hsa-miR-92a-3p | 0.0165 | 0.432 |
has-miR-221-3p | 0.0337 | 0.749 |
hsa-miR-181b-5p | 0.0385 | 0.741 |
miRNA | Overlap | Enrichment | FDR |
---|---|---|---|
Brain development (GO:0007420) | |||
hsa-miR-223-3p | 19 | 1.839 | 0.001298270972 |
hsa-miR-126-3p | 13 | 2.075 | 0.003057508899 |
hsa-miR-138-5p | 18 | 1.617 | 0.007269372947 |
hsa-miR-6740-5p | 11 | 2.103 | 0.007269372947 |
hsa-miR-34a-3p | 14 | 1.734 | 0.0116666655 |
hsa-miR-6806-5p | 10 | 2.018 | 0.01729235795 |
hsa-let-7c-3p | 14 | 1.634 | 0.02040906023 |
hsa-miR-31-3p | 12 | 1.756 | 0.02282151648 |
hsa-miR-9-3p | 14 | 1.593 | 0.0245245798 |
hsa-miR-133b | 12 | 1.639 | 0.03731966297 |
hsa-miR-145-3p | 11 | 1.668 | 0.04186509355 |
hsa-miR-4260 | 11 | 1.686 | 0.04186509355 |
hsa-miR-4699-3p | 12 | 1.591 | 0.04186509355 |
Forebrain development (GO:0030900) | |||
hsa-miR-200c-3p | 22 | 1.96 | 7.98 × 10−5 |
hsa-miR-34a-3p | 12 | 2.253 | 0.004230976391 |
hsa-miR-138-5p | 13 | 1.909 | 0.009118847038 |
hsa-miR-145-3p | 10 | 2.259 | 0.009118847038 |
hsa-miR-200b-3p | 16 | 1.696 | 0.009118847038 |
hsa-miR-31-3p | 10 | 2.226 | 0.009118847038 |
hsa-miR-152-3p | 14 | 1.795 | 0.01067551065 |
hsa-miR-126-3p | 9 | 2.273 | 0.01121765579 |
hsa-miR-9-3p | 11 | 1.995 | 0.01339422516 |
hsa-miR-429 | 13 | 1.69 | 0.02892920941 |
hsa-miR-22-3p | 14 | 1.604 | 0.03007451519 |
hsa-miR-223-3p | 11 | 1.814 | 0.0332969535 |
hsa-let-7c-3p | 10 | 1.9 | 0.03376666551 |
Neurogenesis (GO: 0022008) | |||
hsa-miR-223-3p | 30 | 1.641 | 8.01 × 10−6 |
hsa-miR-1179 | 17 | 1.737 | 0.001535995179 |
hsa-miR-126-3p | 16 | 1.542 | 0.007377225259 |
hsa-miR-127-3p | 9 | 1.791 | 0.02587966401 |
hsa-miR-4632-3p | 9 | 1.627 | 0.04208567062 |
Generation of neurons (GO: 0048699) | |||
hsa-miR-223-3p | 28 | 1.756 | 1.27 × 10−5 |
hsa-miR-1179 | 15 | 1.767 | 0.003310869485 |
hsa-miR-31-3p | 16 | 1.54 | 0.01157149572 |
Nervous system development (R-HSA-9675108) | |||
hsa-miR-100-5p | 28 | 1.599 | 0.0001058059054 |
hsa-miR-652-3p | 17 | 1.569 | 0.01202419931 |
hsa-miR-452-5p | 11 | 1.945 | 0.01686604689 |
Synaptic signaling pathways associated with autism spectrum disorder (WP4539) | |||
hsa-miR-126-3p | 6 | 3.78 | 0.0001311122431 |
hsa-miR-451a | 4 | 3.458 | 0.01312953894 |
hsa-miR-487a-3p | 4 | 3.325 | 0.02304742794 |
hsa-miR-19a-3p | 9 | 2.228 | 0.02807879676 |
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Acerbi da Silva, L.N.; Stumpp, T. Bioinformatic Analysis of Autism-Related miRNAs and Their PoTential as Biomarkers for Autism Epigenetic Inheritance. Genes 2025, 16, 418. https://doi.org/10.3390/genes16040418
Acerbi da Silva LN, Stumpp T. Bioinformatic Analysis of Autism-Related miRNAs and Their PoTential as Biomarkers for Autism Epigenetic Inheritance. Genes. 2025; 16(4):418. https://doi.org/10.3390/genes16040418
Chicago/Turabian StyleAcerbi da Silva, Larissa Naísa, and Taiza Stumpp. 2025. "Bioinformatic Analysis of Autism-Related miRNAs and Their PoTential as Biomarkers for Autism Epigenetic Inheritance" Genes 16, no. 4: 418. https://doi.org/10.3390/genes16040418
APA StyleAcerbi da Silva, L. N., & Stumpp, T. (2025). Bioinformatic Analysis of Autism-Related miRNAs and Their PoTential as Biomarkers for Autism Epigenetic Inheritance. Genes, 16(4), 418. https://doi.org/10.3390/genes16040418