Regulation of Lin28a-miRNA
| العنوان: | Regulation of Lin28a-miRNA |
|---|---|
| المؤلفون: | Hygor N, Araujo, Tanes I, Lima, Dimitrius Santiago P S F, Guimarães, Andre G, Oliveira, Bianca C, Favero-Santos, Renato C S, Branco, Rafaela Mariano, da Silva Araújo, Alvaro F B, Dantas, Alex, Castro, Mara Patrícia T, Chacon-Mikahil, Elaine, Minatel, Murilo V, Geraldo, Everardo Magalhães, Carneiro, Alice C, Rodrigues, Vihang A, Narkar, Leonardo R, Silveira |
| المصدر: | Am J Physiol Cell Physiol |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Mice, Muscle Fibers, Skeletal, Animals, Down-Regulation, RNA-Binding Proteins, PPAR delta, Muscle, Skeletal, Cell Line, Mitochondria, Research Article |
| الوصف: | Lin28a/miRNA let-7b-5p pathway has emerged as a key regulators of energy homeostasis in the skeletal muscle. However, the mechanism through which this pathway is regulated in the skeletal muscle has remained unclear. We have found that 8 wk of aerobic training (Tr) markedly decreased let-7b-5p expression in murine skeletal muscle, whereas high-fat diet (Hfd) increased its expression. Conversely, Lin28a expression, a well-known inhibitor of let-7b-5p, was induced by Tr and decreased by Hfd. Similarly, in human muscle biopsies, Tr increased LIN28 expression and decreased let-7b-5p expression. Bioinformatics analysis of LIN28a DNA sequence revealed that its enrichment in peroxisome proliferator-activated receptor delta (PPARδ) binding sites, which is a well-known metabolic regulator of exercise. Treatment of primary mouse skeletal muscle cells or C2C12 cells with PPARδ activators GW501516 and AICAR increased Lin28a expression. Lin28a and let-7b-5p expression was also regulated by PPARδ coregulators. While PPARγ coactivator-1α (PGC1α) increased Lin28a expression, corepressor NCoR1 decreased its expression. Furthermore, PGC1α markedly reduced the let-7b-5p expression. PGC1α-mediated induction of Lin28a expression was blocked by the PPARδ inhibitor GSK0660. In agreement, Lin28a expression was downregulated in PPARδ knocked-down cells leading to increased let-7b-5p expression. Finally, we show that modulation of the Lin28a-let-7b-5p pathway in muscle cells leads to changes in mitochondrial metabolism in PGC1α dependent fashion. In summary, we demonstrate that Lin28a-let-7b-5p is a direct target of PPARδ in the skeletal muscle, where it impacts mitochondrial respiration. |
| تدمد: | 1522-1563 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=pmid________::995d4f8045bc81785d64f342142d09e6Test https://pubmed.ncbi.nlm.nih.gov/32697599Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.pmid..........995d4f8045bc81785d64f342142d09e6 |
| قاعدة البيانات: | OpenAIRE |
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