|Machado Ivo F, Teodoro JS, Palmeira CM, Rolo AP (2019) Interplay between metformin and miR-378a-3p in cells under hyperglycaemia. MitoFit Preprint Arch doi:10.26124/mitofit:ea19.MiPSchool.0008.|
Abstract: Version 1 (v1) 2019-06-17 doi:10.26124/mitofit:ea19.MiPSchool.0008
Metformin is commonly used for the treatment of Type 2 Diabetes Mellitus (T2DM) being known for its role in the impairment of hepatic gluconeogenesis. However, it has been associated with the upregulation of microRNAs (miRNAs) involved in T2DM and cancer. Recently, it was reported that metformin promoted the expression of miR-378a-3p in HepG2 cells . This miRNA is embedded in the Ppargc1b gene and has been reported to be an important player in the amelioration of obesity through the activation of the pyruvate-phosphoenolpyruvate (PEP) futile cycle in skeletal muscle . Additionally, this miRNA has also been implicated in the regulation of autophagy in skeletal muscle  suggesting that it may also be involved in the removal of damaged mitochondria through mitochondria. In order to study this relation, Sesn2 KD cells were generated given that SESN2 is a stress-inducible protein and it was reported to be crucial in the induction of mitophagy . Additionally, in the current study we explore the importance of miR-378a-3p in the improvement of mitochondrial function in C2C12 cells exposed to hyperglycaemia and demonstrate a possible interplay between metformin and the miRNA in these conditions. - Extended abstract
Machado IF(1), Teodoro JS(1), Palmeira CM(1), Rolo AP(1)
- Dept of Life Sciences and Center for Neurosciences and Cell Biology, Univ of Coimbra. - email@example.com
- Zhou J, Han S, Qian W, Gu Y, Li X, Yang K (2018) Metformin induces miR-378 to downregulate the CDK1, leading to suppression of cell proliferation in hepatocellular carcinoma. OncoTargets Ther 11:4451-4459.
- Zhang Y, Li C, Li H, Song Y, Zhao Y, Zhai L, Wang H, Zhong R, Tang H, Zhu D (2016) MiR-378 activates the pyruvate-PEP futile cycle and enhances lipolysis to ameliorate obesity in mice. EBioMedicine 5:93-104.
- Li Y, Jiang J, Liu W, Wang H, Zhao L, Liu S, Li P, Zhang S, Sun C, Wu Y, Yu S, Li X, Zhang H, Qian H, Zhang D, Guo F, Zhai Q, Ding Q, Wang L, Ying H (2018) microRNA-378 promotes autophagy and inhibits apoptosis in skeletal muscle. Proc Natl Acad Sci U S A 115:E10849-E10858.
- Kumar A, Shaha C (2018) SESN2 facilitates mitophagy by helping Parkin translocation through ULK1 mediated Beclin1 phosphorylation. Sci Rep 8:615.
- Carrer M, Liu N, Grueter CE, Williams AH, Frisard MI, Hulver MW, Bassel-Duby R, Olson EN (2012) Control of mitochondrial metabolism and systemic energy homeostasis by microRNAs 378 and 378*. Proc Natl Acad Sci U S A 109:15330-15335.