title: MicroRNAs Regulate Cellular ATP Levels by Targeting Mitochondrial Energy Metabolism Genes during C2C12 Myoblast Differentiation.
abstract: In our previous study, we identified an miRNA regulatory network involved in energy metabolism in porcine muscle. To better understand the involvement of miRNAs in cellular ATP production and energy metabolism, here we used C2C12 myoblasts, in which ATP levels increase during differentiation, to identify miRNAs modulating these processes. ATP level, miRNA and mRNA microarray expression profiles during C2C12 differentiation into myotubes were assessed. The results suggest 14 miRNAs (miR-423-3p, miR-17, miR-130b, miR-301a/b, miR-345, miR-15a, miR-16a, miR-128, miR-615, miR-1968, miR-1a/b, and miR-194) as cellular ATP regulators targeting genes involved in mitochondrial energy metabolism (Cox4i2, Cox6a2, Ndufb7, Ndufs4, Ndufs5, and Ndufv1) during C2C12 differentiation. Among these, miR-423-3p showed a high inverse correlation with increasing ATP levels. Besides having implications in promoting cell growth and cell cycle progression, its function in cellular ATP regulation is yet unknown. Therefore, miR-423-3p was selected and validated for the function together with its potential target, Cox6a2. Overexpression of miR-423-3p in C2C12 myogenic differentiation lead to decreased cellular ATP level and decreased expression of Cox6a2 compared to the negative control. These results suggest miR-423-3p as a novel regulator of ATP/energy metabolism by targeting Cox6a2.
authors.affiliation: Research Institute for the Biology of Farm Animals (FBN), Research unit Functional Genomics, Dummerstorf, Germany.
authors.forename: Puntita
authors.initials: P
authors.lastname: Siengdee
authors.affiliation: Research Institute for the Biology of Farm Animals (FBN), Research Unit Molecular Biology, Dummerstorf, Germany.
authors.forename: Nares
authors.initials: N
authors.lastname: Trakooljul
authors.affiliation: Research Institute for the Biology of Farm Animals (FBN), Research Unit Molecular Biology, Dummerstorf, Germany.
authors.forename: Eduard
authors.initials: E
authors.lastname: Murani
authors.affiliation: Research Institute for the Biology of Farm Animals (FBN), Research unit Functional Genomics, Dummerstorf, Germany.
authors.forename: Manfred
authors.initials: M
authors.lastname: Schwerin
authors.affiliation: Research Institute for the Biology of Farm Animals (FBN), Research Unit Molecular Biology, Dummerstorf, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Wimmers
authors.affiliation: Research Institute for the Biology of Farm Animals (FBN), Research unit Functional Genomics, Dummerstorf, Germany.
authors.forename: Siriluck
authors.initials: S
authors.lastname: Ponsuksili
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D004734:Energy Metabolism / Q000502:physiology*; D051379:Mice; D035683:MicroRNAs / Q000096:biosynthesis*; D008931:Mitochondria, Muscle / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000096:biosynthesis*; D009124:Muscle Proteins / Q000096:biosynthesis*; D032448:Myoblasts, Skeletal / Q000166:cytology / Q000378:metabolism*
chemical_list: D035683:MicroRNAs; D024101:Mitochondrial Proteins; D009124:Muscle Proteins; D000255:Adenosine Triphosphate