miR-378a-3p Participates in Metformin’s Mechanism of Action on C2C12 Cells under Hyperglycemia
Open Access
- 7 January 2021
- journal article
- research article
- Published by MDPI AG in International Journal of Molecular Sciences
- Vol. 22 (2), 541
- https://doi.org/10.3390/ijms22020541
Abstract
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 (p < 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 Tfam. Finally, mitophagy, an autophagic process responsible for the selective degradation of mitochondria, was found to be induced by miR-378a-3p (p < 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.Funding Information
- European Regional Development Fund (CENTRO-01-0145-FEDER-000012- HealthyAging2020)
- Fundação para a Ciência e a Tecnologia (POCI-01-0145-FEDER-016770, UID/NEU/04539/2013, HEALTHYAGING 2020 CENTRO-01- 0145-FEDER-000012, CEECIND/4400/2017)
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