MiR-96-5p Induced by Palmitic Acid Suppresses the Myogenic Differentiation of C2C12 Myoblasts by Targeting FHL1.
Skeletal myogenesis is a multi-stage process that includes the cell cycle exit, myogenic transcriptional activation, and morphological changes to form multinucleated myofibers. Recent studies have shown that saturated fatty acids (SFA) and miRNAs play crucial roles in myogenesis and muscle homeostasis. Nevertheless, the target molecules and myogenic regulatory mechanisms of miRNAs are largely unknown, particularly when myogenesis is dysregulated by SFA deposition. This study investigated the critical role played by miR-96-5p on the myogenic differentiation in C2C12 myoblasts. Long-chain SFA palmitic acid (PA) significantly reduced FHL1 expression and inhibited the myogenic differentiation of C2C12 myoblasts but induced miR-96-5p expression. The knockdown of FHL1 by siRNA stimulated cell proliferation and inhibited myogenic differentiation of myoblasts. Interestingly, miR-96-5p suppressed FHL1 expression by directly targeting the 3'UTR of FHL1 mRNA. The transfection of an miR-96-5p mimic upregulated the expressions of cell cycle-related genes, such as PCNA, CCNB1, and CCND1, and increased myoblast proliferation. Moreover, the miR-96-5p mimic inhibited the expressions of myogenic factors, such as myoblast determination protein (MyoD), myogenin (MyoG), myocyte enhancer factor 2C (MEF2C), and myosin heavy chain (MyHC), and dramatically impeded differentiation and fusion of myoblasts. Overall, this study highlights the role of miR-96-5p in myogenesis via FHL1 suppression and suggests a novel regulatory mechanism for myogenesis mediated by miRNA in a background of obesity.
['Nguyen|Mai Thi|MT|0000-0002-6469-9514', 'Min|Kyung-Ho|KH|', 'Lee|Wan|W|0000-0002-5181-2135']
D020413:3' Untranslated Regions D000818:Animals D002454:Cell Differentiation D002460:Cell Line D005455:Fluorescent Antibody Technique D015151:Immunoblotting D047908:Intracellular Signaling Peptides and Proteins D060588:LIM Domain Proteins D064326:MEF2 Transcription Factors D051379:Mice D035683:MicroRNAs D024510:Muscle Development D009124:Muscle Proteins D017570:MyoD Protein D018008:Myogenin D019308:Palmitic Acid D012333:RNA, Messenger D020133:Reverse Transcriptase Polymerase Chain Reaction
miR-96-5p palmitic acid differentiation FHL1 microRNA