Cited by 12MicroRNA in disease regulationSpinal Cord Injury ResearchCell death mechanisms and regulation

MicroRNA-138-5p Targets Pro-Apoptotic Factors and Favors Neural Cell Survival: Analysis in the Injured Spinal Cord

Open access
Maza, Rodrigo M., Barreda-Manso, María Asunción, Reigada, David, Silván, Ágata, Muñoz-Galdeano, Teresa, Soto, Altea, del Águila, Ángela, Nieto-Díaz, Manuel·2022·Biomedicines

Abstract

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

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    The cited work was retracted on 2022-03-25 (notice 10.1016/j.biopha.2022.112849), before this paper was published (2022-06-30).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

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Research works printed but not linked: 3

  1. Yi, 2016, miR-124 mediated neuron apoptosis in spinal cord injury by targeting the 3’ UTR end of calpain, Int. J. Clin. Exp. Pathol., 15, 5989
  2. Maza, R.M., Reinecke, H., Muñoz-Galdeano, T., Reigada, D., Elvira, C., Tínez-Campos, E., Gallardo, A., Bosch, P., Rodriguez-Hernandez, J., and Nieto-Diaz, M. Evaluation of RVG29-Functionalized polyethylenimines for neural cell transfection. Proceedings of the Poster Communication to the 10th Cajal Conference, Cuenca, Spain. Available online: https://osf.io/yqn58/.
  3. Uceta-García, M. (2020). Therapeutic Potential of miR-135a-5p and miR-138-5p for the Treatment of Spinal Cord Injury: Analsysis of Expression Changes. [Master’s Thesis]. Available online: https://osf.io/yqn58/.

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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.
Venue
Biomedicines
Publisher
MDPI AG
Published
2022-06-30
Volume
10
Issue
7
Pages
1559
ISSN
2227-9059 (ISSN-L)
OpenAlex
W4283739933
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
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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