A project by the Molecular Neuroprotection Group of the Research Unit of the Hospital Nacional de Parapléjicos (Toledo, Spain)
Title:
MicroRNA-138-5p targets pro-apoptotic factors and favours neural cell survival: analysis in the injured spinal cord.
Authors:
Rodrigo M. Maza, M. Asunción Barreda-Manso, David Reigada, Agata Silván, Altea Soto, Teresa Muñoz-Galdeano, Ángela del Águila, Manuel Nieto-Díaz.
Journal: Biomedicines
Summary:
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.
Components:
- Image repository
- Supplementary material.
- Bibliography
Funding and acknowledgements:
Research was funded by grants from the Fundación Tatiana Pérez de Guzmán el Bueno and the Council of Education, Culture and Sports of the Regional Government of Castilla La Mancha (Spain) and Co-financed by the European Union (FEDER) "A way to make Europe" (project reference SBPLY/17/000376). Altea Soto is funded by the Council of Education, Culture and Sports of the Regional Government of Castilla La Mancha (Spain). M. Asunción Barreda-Manso is funded by the Council of Health of the Regional Government of Castilla La Mancha (Spain).
