Dysregulation of MicroRNAs and Target Genes Networks in Peripheral Blood of Patients With Sporadic Amyotrophic Lateral Sclerosis.
Open accessAbstract
Amyotrophic Lateral Sclerosis (ALS) is a progressive and fatal neurodegenerative disease. While genetics and other factors contribute to ALS pathogenesis, critical knowledge is still missing and validated biomarkers for monitoring the disease activity have not yet been identified. To address those aspects we performed this study with the primary aim of identifying possible miRNAs/mRNAs dysregulation associated with the sporadic form of the disease (sALS). Additionally, we explored miRNAs as modulating factors of the observed clinical features. Study included 56 sALS and 20 healthy controls (HC). We analyzed the peripheral blood samples of sALS patients and HC with a High-Throughput Next-generation Sequencing followed by an integrated bioinformatics/biostatistics analysis. Results showed that 38 miRNAs (let-7a-5p, let-7d-5p, let-7f-5p, let-7g-5p, let-7i-5p, miR-103a-3p, miR-106b-3p, miR-128-3p, miR-130a-3p, miR-130b-3p, miR-144-5p, miR-148a-3p, miR-148b-3p, miR-15a-5p, miR-15b-5p, miR-151a-5p, miR-151b, miR-16-5p, miR-182-5p, miR-183-5p, miR-186-5p, miR-22-3p, miR-221-3p, miR-223-3p, miR-23a-3p, miR-26a-5p, miR-26b-5p, miR-27b-3p, miR-28-3p, miR-30b-5p, miR-30c-5p, miR-342-3p, miR-425-5p, miR-451a, miR-532-5p, miR-550a-3p, miR-584-5p, miR-93-5p) were significantly downregulated in sALS. We also found that different miRNAs profiles characterized the bulbar/spinal onset and the progression rate. This observation supports the hypothesis that miRNAs may impact the phenotypic expression of the disease. Genes known to be associated with ALS (e.g. PARK7, C9orf72, ALS2, MATR3, SPG11, ATXN2) were confirmed dysregulated in our study, as well as we identified other potential candidate genes like LGALS3 (implicated in neuroinflammation) and PRKCD (activated in mitochondrial-induced apoptosis). Some of the downregulated genes are involved in molecular bindings to ions (i.e. metals, zinc, magnesium) and in ions-related functions. The genes that we found upregulated genes involved in the immune response, oxidation-reduction and apoptosis. These findings may have important implication for the monitoring e.g. of sALS progression and therefore represent a significant advance in the elucidation of the disease’s underlying molecular mechanisms. The extensive multidisciplinary approach we applied in this study was critically important for its success, especially in complex disorders such as sALS, wherein access to genetic background is a major limitation.
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Many studies have shown a close relationship between microRNAs and mRNAs in disease regulation, particularly the negative feedback regulation of targeted mRNAs by their miRNAs.
“Many other studies have shown a close relationship between microRNAs and mRNAs in disease regulation, particularly the negative feedback regulation of targeted mRNAs by their miRNAs [13–14]”
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- Authors
- Liguori, M., Nuzziello, N., Introna, A., Consiglio, A., Licciulli, F., D’Errico, E., Scarafino, A., Distaso, E., & Simone, I. L.
- Affiliations
- Institute of Biomedical Technologies (IT)
- University of Bari Aldo Moro (IT)
- Corresponding author
- Liguori, Maria
- ORCID
- Venue
- Frontiers in Molecular Neuroscience
- Publisher
- Frontiers Media SA
- Published
- 2018-08-28
- Volume
- 11
- Pages
- 288-288
- ISSN
- 1662-5099 (ISSN-L)
- PMC
- PMC6121079
- OpenAlex
- W2889233894
- Cited by
- 131
- References
- 83
- Citations by year
- 2026: 6 · 2025: 15 · 2024: 20 · 2023: 12 · 2022: 24 · 2021: 13 · 2020: 24 · 2019: 14 · 2018: 3
- FWCI
- 9.15
- Type
- journal article
- Language
- en
- Update notices
- corrigendum (2019-01-10)
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Molecular Neuroscience (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- CINECA IRIS Institutional Research Information System (University of Bari Aldo Moro) (submittedVersion, other-oa)
- Topics
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Keywords
- amyotrophic lateral sclerosis, sporadic ALS, microRNA dysregulation, peripheral blood, miRNA-mRNA regulatory network, let-7 family, miR-146a, miR-15a-5p, miR-15b-5p, miR-16-5p, miR-182-5p, miR-183-5p, miR-186-5p, miR-22-3p, miR-221-3p, miR-223-3p, miR-26a-5p, miR-26b-5p, miR-27b-3p, miR-28-3p, miR-30b-5p, miR-30c-5p, miR-342
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