miR-378a-3p Participates in Metformin’s Mechanism of Action on C2C12 Cells under Hyperglycemia
Metformin is the most used biguanide drug for the treatment of type 2 diabetes mellitus. Despite being mostly known for its hepatic anti-gluconeogenic effect, it is also known to modulate microRNAs (miRNAs, miRs) associated with metabolic diseases. The latter mechanism could be relevant for better u...
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| Format: | Article |
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MDPI AG
2021-01-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/2/541 |
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| author | Ivo F. Machado João S. Teodoro Ana C. Castela Carlos M. Palmeira Anabela P. Rolo |
| author_facet | Ivo F. Machado João S. Teodoro Ana C. Castela Carlos M. Palmeira Anabela P. Rolo |
| author_sort | Ivo F. Machado |
| collection | DOAJ |
| description | Metformin is the most used biguanide drug for the treatment of type 2 diabetes mellitus. Despite being mostly known for its hepatic anti-gluconeogenic effect, it is also known to modulate microRNAs (miRNAs, miRs) associated with metabolic diseases. The latter mechanism could be relevant for better understanding metformin’s mechanisms underlying its biological effects. In the current work, we found that metformin increases miR-378a-3p expression (<i>p</i> < 0.002) in C2C12 myoblasts previously exposed to hyperglycemic conditions. While the inhibition of miR-378a-3p was shown to impair metformin’s effect in ATP production, PEPCK activity and the expression of <i>Tfam</i>. Finally, mitophagy, an autophagic process responsible for the selective degradation of mitochondria, was found to be induced by miR-378a-3p (<i>p</i> < 0.04). miR-378a-3p stimulated mitophagy through a process independent of sestrin-2 (SESN2), a stress-responsible protein that has been recently demonstrated to positively modulate mitophagy. Our findings provide novel insights into an alternative mechanism of action of metformin involving miR-378a-3, which can be used in the future for the development of improved therapeutic strategies against metabolic diseases. |
| first_indexed | 2024-03-09T05:46:42Z |
| format | Article |
| id | doaj.art-ffe6f496fe114f6296314d9d552136bf |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T05:46:42Z |
| publishDate | 2021-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-ffe6f496fe114f6296314d9d552136bf2023-12-03T12:21:13ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-01-0122254110.3390/ijms22020541miR-378a-3p Participates in Metformin’s Mechanism of Action on C2C12 Cells under HyperglycemiaIvo F. Machado0João S. Teodoro1Ana C. Castela2Carlos M. Palmeira3Anabela P. Rolo4Department of Life Sciences, Faculty of Sciences and Technology, University of Coimbra, 3000-456 Coimbra, PortugalDepartment of Life Sciences, Faculty of Sciences and Technology, University of Coimbra, 3000-456 Coimbra, PortugalDepartment of Life Sciences, Faculty of Sciences and Technology, University of Coimbra, 3000-456 Coimbra, PortugalDepartment of Life Sciences, Faculty of Sciences and Technology, University of Coimbra, 3000-456 Coimbra, PortugalDepartment of Life Sciences, Faculty of Sciences and Technology, University of Coimbra, 3000-456 Coimbra, PortugalMetformin is the most used biguanide drug for the treatment of type 2 diabetes mellitus. Despite being mostly known for its hepatic anti-gluconeogenic effect, it is also known to modulate microRNAs (miRNAs, miRs) associated with metabolic diseases. The latter mechanism could be relevant for better understanding metformin’s mechanisms underlying its biological effects. In the current work, we found that metformin increases miR-378a-3p expression (<i>p</i> < 0.002) in C2C12 myoblasts previously exposed to hyperglycemic conditions. While the inhibition of miR-378a-3p was shown to impair metformin’s effect in ATP production, PEPCK activity and the expression of <i>Tfam</i>. Finally, mitophagy, an autophagic process responsible for the selective degradation of mitochondria, was found to be induced by miR-378a-3p (<i>p</i> < 0.04). miR-378a-3p stimulated mitophagy through a process independent of sestrin-2 (SESN2), a stress-responsible protein that has been recently demonstrated to positively modulate mitophagy. Our findings provide novel insights into an alternative mechanism of action of metformin involving miR-378a-3, which can be used in the future for the development of improved therapeutic strategies against metabolic diseases.https://www.mdpi.com/1422-0067/22/2/541miR-378a-3pmetforminmitochondriamitophagyC2C12 |
| spellingShingle | Ivo F. Machado João S. Teodoro Ana C. Castela Carlos M. Palmeira Anabela P. Rolo miR-378a-3p Participates in Metformin’s Mechanism of Action on C2C12 Cells under Hyperglycemia International Journal of Molecular Sciences miR-378a-3p metformin mitochondria mitophagy C2C12 |
| title | miR-378a-3p Participates in Metformin’s Mechanism of Action on C2C12 Cells under Hyperglycemia |
| title_full | miR-378a-3p Participates in Metformin’s Mechanism of Action on C2C12 Cells under Hyperglycemia |
| title_fullStr | miR-378a-3p Participates in Metformin’s Mechanism of Action on C2C12 Cells under Hyperglycemia |
| title_full_unstemmed | miR-378a-3p Participates in Metformin’s Mechanism of Action on C2C12 Cells under Hyperglycemia |
| title_short | miR-378a-3p Participates in Metformin’s Mechanism of Action on C2C12 Cells under Hyperglycemia |
| title_sort | mir 378a 3p participates in metformin s mechanism of action on c2c12 cells under hyperglycemia |
| topic | miR-378a-3p metformin mitochondria mitophagy C2C12 |
| url | https://www.mdpi.com/1422-0067/22/2/541 |
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