MicroRNA-138-5p Targets Pro-Apoptotic Factors and Favors Neural Cell Survival: Analysis in the Injured Spinal Cord
Open accessAbstract
The central nervous system microRNA miR-138-5p has attracted much attention in cancer research because it inhibits pro-apoptotic genes including CASP3. We hypothesize that miR-138-5p downregulation after SCI leads to overexpression of pro-apoptotic genes, sensitizing neural cells to noxious stimuli. This study aimed to identify miR-138-5p targets among pro-apoptotic genes overexpressed following SCI and to confirm that miR-138-5p modulates cell death in neural cells. Gene expression and histological analyses revealed that the drop in miR-138-5p expression after SCI is due to the massive loss of neurons and oligodendrocytes and its downregulation in neurons. Computational analyses identified 176 potential targets of miR-138-5p becoming dysregulated after SCI, including apoptotic proteins CASP-3 and CASP-7, and BAK. Reporter, RT-qPCR, and immunoblot assays in neural cell cultures confirmed that miR-138-5p targets their 3′UTRs, reduces their expression and the enzymatic activity of CASP-3 and CASP-7, and protects cells from apoptotic stimuli. Subsequent RT-qPCR and histological analyses in a rat model of SCI revealed that miR-138-5p downregulation correlates with the overexpression of its pro-apoptotic targets. Our results suggest that the downregulation of miR-138-5p after SCI may have deleterious effects on neural cells, particularly on spinal neurons.
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Cites a retracted work: 10.1016/j.biopha.2018.03.040
MajorThe cited work was retracted on 2022-03-25 (notice 10.1016/j.biopha.2022.112849), before this paper was published (2022-06-30). Its authors could have known.
Cited work 10.1016/j.biopha.2018.03.040 · retracted 2022-03-25 · notice 10.1016/j.biopha.2022.112849 · this paper published 2022-06-30
“Zheng, 2018, Astragalus polysaccharide protects hypoxia-induced injury by up-regulation of miR-138 in rat neural stem cells, Biomed. Pharmacoth., 102, 295, 10.1016/j.biopha.2018.03.040”
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MiR-200c regulates ROS-induced apoptosis in murine BV-2 cells by targeting FAP-1
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MiR-137–3p rescue motoneuron death by targeting calpain-2
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MicroRNA‑138‑5p regulates the development of spinal cord injury by targeting SIRT1
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Increased expression of CDK11p58 and cyclin D3 following spinal cord injury in rats
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miRNA-138 regulates MLK3/JNK/MAPK pathway to protect BV-2 cells from H2O2-induced apoptosis
Ren, R., Chen, S. D., Fan, J., Zhang, G., & Jia-Long, L. I. (2018) · Bratislavské lekárske listy/Bratislava medical journal · doi:10.4149/bll_2018_053 · Cited by 20 · see citing works
Vimentin Regulates Neuroplasticity in Transected Spinal Cord Rats Associated with micRNA138
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The nuclear matrix protein Matr3 regulates processing of the synaptic microRNA-138-5p
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Serotonin 2C receptor alternative splicing in a spinal cord injury model
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Flagged first, then by citations
5 of the 108 references couldn’t be matched to a known paper.
Research works printed but not linked: 3
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miRNA Expression Profile in Primary Limbal Epithelial Cells of Aniridia Patients
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MiR-138-5p Upregulation during Neuronal Maturation Parallels with an Increase in Neuronal Survival
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Muñoz‐Galdeano, T., Reigada, D., Gamarra, M., Soto, A., Barreda-Manso, M. A., Novillo, I., Nieto‐Díaz, M., & Maza, R. M. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms252212374 · Cited by 2 · see citing works
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- Authors
- Maza, R. M., Barreda-Manso, M. A., Reigada, D., Silván, Á., Muñoz-Galdeano, T., Soto, A., del Águila, Á., & Nieto-Díaz, M.
- Affiliations
- Servicio de Salud de Castilla La Mancha (ES)
- Molecular Neuroprotection Group, Research Unit, National Hospital for Paraplegics (SESCAM), 45071 Toledo, Spain
- University of Copenhagen (DK)
- Duke Medical Center (US)
- Corresponding author
- Maza, Rodrigo M.
- ORCID
- Venue
- Biomedicines
- Publisher
- MDPI AG
- Published
- 2022-06-30
- Volume
- 10
- Issue
- 7
- Pages
- 1559
- ISSN
- 2227-9059 (ISSN-L)
- PMC
- PMC9312482
- OpenAlex
- W4283739933
- Semantic Scholar
- b4a5463db28aec0a22bd51fe752e495dd38ce0ba
- Cited by
- 12
- References
- 108
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 1 · 2023: 4
- FWCI
- 0.89
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Biomedicines (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- OSF Preprints (OSF Preprints) (submittedVersion)
- Funders
- Fundación Tatiana Pérez de Guzmán el Bueno (Neurociencia 2016) (SBPLY/17/000376, SBPLY/21/180501/000097)
- Council of Education, Culture, and Sports of the Regional Government of Castilla La Mancha (Spain) (SBPLY/17/000376, SBPLY/21/180501/000097)
- European Union (FEDER) “A way to make Europe” (SBPLY/17/000376, SBPLY/21/180501/000097)
- Council of Health of the Regional Government of Castilla La Mancha (Spain) (SBPLY/17/000376, SBPLY/21/180501/000097)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Health Sciences › Medicine › Pathology and Forensic Medicine › Spinal Cord Injury Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Keywords
- miR-138-5p, spinal cord injury, apoptosis, pro-apoptotic genes, Bak, 3' UTR target, oligodendrocyte loss, neuronal survival, microRNA downregulation, neuroprotection
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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