MicroRNA-138-5p Targets Pro-Apoptotic Factors and Favors Neural Cell Survival: Analysis in the Injured Spinal Cord
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....
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MDPI AG
2022-06-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/10/7/1559 |
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| author | Rodrigo M. Maza María Asunción Barreda-Manso David Reigada Ágata Silván Teresa Muñoz-Galdeano Altea Soto Ángela del Águila Manuel Nieto-Díaz |
| author_facet | Rodrigo M. Maza María Asunción Barreda-Manso David Reigada Ágata Silván Teresa Muñoz-Galdeano Altea Soto Ángela del Águila Manuel Nieto-Díaz |
| author_sort | Rodrigo M. Maza |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T10:22:33Z |
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| id | doaj.art-bc7faf3326e64ae2b14a8c259184571d |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-09T10:22:33Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-bc7faf3326e64ae2b14a8c259184571d2023-12-01T21:55:53ZengMDPI AGBiomedicines2227-90592022-06-01107155910.3390/biomedicines10071559MicroRNA-138-5p Targets Pro-Apoptotic Factors and Favors Neural Cell Survival: Analysis in the Injured Spinal CordRodrigo M. Maza0María Asunción Barreda-Manso1David Reigada2Ágata Silván3Teresa Muñoz-Galdeano4Altea Soto5Ángela del Águila6Manuel Nieto-Díaz7Molecular Neuroprotection Group, Research Unit, National Hospital for Paraplegics (SESCAM), 45071 Toledo, SpainMolecular Neuroprotection Group, Research Unit, National Hospital for Paraplegics (SESCAM), 45071 Toledo, SpainMolecular Neuroprotection Group, Research Unit, National Hospital for Paraplegics (SESCAM), 45071 Toledo, SpainMolecular Neuroprotection Group, Research Unit, National Hospital for Paraplegics (SESCAM), 45071 Toledo, SpainMolecular Neuroprotection Group, Research Unit, National Hospital for Paraplegics (SESCAM), 45071 Toledo, SpainMolecular Neuroprotection Group, Research Unit, National Hospital for Paraplegics (SESCAM), 45071 Toledo, SpainMolecular Neuroprotection Group, Research Unit, National Hospital for Paraplegics (SESCAM), 45071 Toledo, SpainMolecular Neuroprotection Group, Research Unit, National Hospital for Paraplegics (SESCAM), 45071 Toledo, SpainThe 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.https://www.mdpi.com/2227-9059/10/7/1559neuroprotectionspinal cord injurymiR-based therapiescell death |
| spellingShingle | Rodrigo M. Maza María Asunción Barreda-Manso David Reigada Ágata Silván Teresa Muñoz-Galdeano Altea Soto Ángela del Águila Manuel Nieto-Díaz MicroRNA-138-5p Targets Pro-Apoptotic Factors and Favors Neural Cell Survival: Analysis in the Injured Spinal Cord Biomedicines neuroprotection spinal cord injury miR-based therapies cell death |
| title | MicroRNA-138-5p Targets Pro-Apoptotic Factors and Favors Neural Cell Survival: Analysis in the Injured Spinal Cord |
| title_full | MicroRNA-138-5p Targets Pro-Apoptotic Factors and Favors Neural Cell Survival: Analysis in the Injured Spinal Cord |
| title_fullStr | MicroRNA-138-5p Targets Pro-Apoptotic Factors and Favors Neural Cell Survival: Analysis in the Injured Spinal Cord |
| title_full_unstemmed | MicroRNA-138-5p Targets Pro-Apoptotic Factors and Favors Neural Cell Survival: Analysis in the Injured Spinal Cord |
| title_short | MicroRNA-138-5p Targets Pro-Apoptotic Factors and Favors Neural Cell Survival: Analysis in the Injured Spinal Cord |
| title_sort | microrna 138 5p targets pro apoptotic factors and favors neural cell survival analysis in the injured spinal cord |
| topic | neuroprotection spinal cord injury miR-based therapies cell death |
| url | https://www.mdpi.com/2227-9059/10/7/1559 |
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