BMB Reports

Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
권호 표지
DOI QR코드

DOI QR Code

MiR-183-5p induced by saturated fatty acids regulates the myogenic differentiation by directly targeting FHL1 in C2C12 myoblasts

  • Nguyen, Mai Thi (Department of Biochemistry, Dongguk University College of Medicine) ;
  • Min, Kyung-Ho (Department of Biochemistry, Dongguk University College of Medicine) ;
  • Lee, Wan (Department of Biochemistry, Dongguk University College of Medicine)
  • Received : 2020.08.24
  • Accepted : 2020.10.22
  • Published : 2020.11.30
Download PDF
⟨ Previous Next ⟩

Abstract

Skeletal myogenesis is a complex process that is finely regulated by myogenic transcription factors. Recent studies have shown that saturated fatty acids (SFA) can suppress the activation of myogenic transcription factors and impair the myogenic differentiation of progenitor cells. Despite the increasing evidence of the roles of miRNAs in myogenesis, the targets and myogenic regulatory mechanisms of miRNAs are largely unknown, particularly when myogenesis is dysregulated by SFA deposition. This study examined the implications of SFA-induced miR-183-5p on the myogenic differentiation in C2C12 myoblasts. Long-chain SFA palmitic acid (PA) drastically reduced myogenic transcription factors, such as myoblast determination protein (MyoD), myogenin (MyoG), and myocyte enhancer factor 2C (MEF2C), and inhibited FHL1 expression and myogenic differentiation of C2C12 myoblasts, accompanied by the induction of miR-183-5p. The knockdown of FHL1 by siRNA inhibited myogenic differentiation of myoblasts. Interestingly, miR-183-5p inversely regulated the expression of FHL1, a crucial regulator of skeletal myogenesis, by targeting the 3'UTR of FHL1 mRNA. Furthermore, the transfection of miR-183-5p mimic suppressed the expression of MyoD, MyoG, MEF2C, and MyHC, and impaired the differentiation and myotube formation of myoblasts. Overall, this study highlights the role of miR-183-5p in myogenic differentiation through FHL1 repression and suggests a novel miRNA-mediated mechanism for myogenesis in a background of obesity.

Keywords

References

  1. Chal J and Pourquie O (2017) Making muscle: skeletal myogenesis in vivo and in vitro. Development 144, 2104-2122 https://doi.org/10.1242/dev.151035
  2. Asfour HA, Allouh MZ and Said RS (2018) Myogenic regulatory factors: The orchestrators of myogenesis after 30 years of discovery. Exp Biol Med (Maywood) 243, 118-128 https://doi.org/10.1177/1535370217749494
  3. Benarroch L, Bonne G, Rivier F and Hamroun D (2019) The 2020 version of the gene table of neuromuscular disorders (nuclear genome). Neuromuscul Disord 29, 980-1018 https://doi.org/10.1016/j.nmd.2019.10.010
  4. Akhmedov D and Berdeaux R (2013) The effects of obesity on skeletal muscle regeneration. Front Physiol 4, 371 https://doi.org/10.3389/fphys.2013.00371
  5. Chang YC, Liu HW, Chen YT, Chen YA, Chen YJ and Chang SJ (2018) Resveratrol protects muscle cells against palmitate-induced cellular senescence and insulin resistance through ameliorating autophagic flux. J Food Drug Anal 26, 1066-1074 https://doi.org/10.1016/j.jfda.2018.01.006
  6. Zhang G, Chen X, Lin L, Wen C and Rao S (2012) [Effects of fatty acids on proliferation and differentiation of myoblast]. Wei Sheng Yan Jiu 41, 883-888
  7. Saini A, Sharples AP, Al-Shanti N and Stewart CE (2017) Omega-3 fatty acid EPA improves regenerative capacity of mouse skeletal muscle cells exposed to saturated fat and inflammation. Biogerontology 18, 109-129 https://doi.org/10.1007/s10522-016-9667-3
  8. Xu D, Jiang Z, Sun Z et al (2019) Mitochondrial dysfunction and inhibition of myoblast differentiation in mice with high-fat-diet-induced pre-diabetes. J Cell Physiol 234, 7510-7523 https://doi.org/10.1002/jcp.27512
  9. Krol J, Loedige I and Filipowicz W (2010) The widespread regulation of microRNA biogenesis, function and decay. Nat Rev Genet 11, 597-610 https://doi.org/10.1038/nrg2843
  10. Saliminejad K, Khorram Khorshid HR, Soleymani Fard S and Ghaffari SH (2019) An overview of microRNAs: Biology, functions, therapeutics, and analysis methods. J Cell Physiol 234, 5451-5465 https://doi.org/10.1002/jcp.27486
  11. Mok GF, Lozano-Velasco E and Münsterberg A (2017) microRNAs in skeletal muscle development. Semin Cell Dev Biol 72, 67-76 https://doi.org/10.1016/j.semcdb.2017.10.032
  12. Ji C and Guo X (2019) The clinical potential of circulating microRNAs in obesity. Nat Rev Endocrinol 15, 731-743 https://doi.org/10.1038/s41574-019-0260-0
  13. Ortiz-Dosal A, Rodil-Garcia P and Salazar-Olivo LA (2019) Circulating microRNAs in human obesity: a systematic review. Biomarkers 24, 499-509 https://doi.org/10.1080/1354750x.2019.1606279
  14. Kadrmas JL and Beckerle MC (2004) The LIM domain: from the cytoskeleton to the nucleus. Nat Rev Mol Cell Biol 5, 920-931 https://doi.org/10.1038/nrm1499
  15. Wei X and Zhang H (2020) Four and a half LIM domains protein 1 can be as a double-edged sword in cancer progression. Cancer Biol Med 17, 270-281 https://doi.org/10.20892/j.issn.2095-3941.2019.0420
  16. Windpassinger C, Schoser B, Straub V et al (2008) An X-linked myopathy with postural muscle atrophy and generalized hypertrophy, termed XMPMA, is caused by mutations in FHL1. Am J Hum Genet 82, 88-99 https://doi.org/10.1016/j.ajhg.2007.09.004
  17. Chen DH, Raskind WH, Parson WW et al (2010) A novel mutation in FHL1 in a family with X-linked scapuloperoneal myopathy: phenotypic spectrum and structural study of FHL1 mutations. J Neurol Sci 296, 22-29 https://doi.org/10.1016/j.jns.2010.06.017
  18. Gueneau L, Bertrand AT, Jais JP et al (2009) Mutations of the FHL1 gene cause Emery-Dreifuss muscular dystrophy. Am J Hum Genet 85, 338-353 https://doi.org/10.1016/j.ajhg.2009.07.015
  19. Cowling BS, McGrath MJ, Nguyen MA et al (2008) Identification of FHL1 as a regulator of skeletal muscle mass: implications for human myopathy. J Cell Biol 183, 1033-1048 https://doi.org/10.1083/jcb.200804077
  20. Lee JY, Chien IC, Lin WY et al (2012) Fhl1 as a downstream target of Wnt signaling to promote myogenesis of C2C12 cells. Mol Cell Biochem 365, 251-262 https://doi.org/10.1007/s11010-012-1266-2
  21. Domenighetti AA, Chu PH, Wu T et al (2014) Loss of FHL1 induces an age-dependent skeletal muscle myopathy associated with myofibrillar and intermyofibrillar disorganization in mice. Hum Mol Genet 23, 209-225 https://doi.org/10.1093/hmg/ddt412
  22. Ding J, Cong YF, Liu B, Miao J and Wang L (2018) Aberrant protein turn-over associated with myofibrillar disorganization in FHL1 knockout mice. Front Genet 9, 273 https://doi.org/10.3389/fgene.2018.00273
  23. Abreu P, Leal-Cardoso JH, Ceccatto VM and Hirabara SM (2017) Regulation of muscle plasticity and trophism by fatty acids: A short review. Rev Assoc Med Bras (1992) 63, 148-155 https://doi.org/10.1590/1806-9282.63.02.148
  24. Han S, Cui C, He H et al (2019) FHL1 regulates myoblast differentiation and autophagy through its interaction with LC3. J Cell Physiol 235, 4667-4678 https://doi.org/10.1002/jcp.29345
  25. Zhao Y, Chen M, Lian D et al (2019) Non-coding RNA regulates the myogenesis of skeletal muscle satellite cells, injury repair and diseases. Cells 8, 988 https://doi.org/10.3390/cells8090988
  26. Dambal S, Shah M, Mihelich B and Nonn L (2015) The microRNA-183 cluster: the family that plays together stays together. Nucleic Acids Res 43, 7173-7188 https://doi.org/10.1093/nar/gkv703
  27. Shao X, Wang M, Wei X et al (2016) Peroxisome proliferator-activated receptor-gamma: master regulator of adipogenesis and obesity. Curr Stem Cell Res Ther 11, 282-289 https://doi.org/10.2174/1574888X10666150528144905
  28. Lefterova MI, Zhang Y, Steger DJ et al (2008) PPARgamma and C/EBP factors orchestrate adipocyte biology via adjacent binding on a genome-wide scale. Genes Dev 22, 2941-2952 https://doi.org/10.1101/gad.1709008
  29. John E, Wienecke-Baldacchino A, Liivrand M, Heinaniemi M, Carlberg C and Sinkkonen L (2012) Dataset integration identifies transcriptional regulation of microRNA genes by PPARgamma in differentiating mouse 3T3-L1 adipocytes. Nucleic Acids Res 40, 4446-4460 https://doi.org/10.1093/nar/gks025
  30. Yang WM, Min KH and Lee W (2016) MicroRNA expression analysis in the liver of high fat diet-induced obese mice. Data Brief 9, 1155-1159 https://doi.org/10.1016/j.dib.2016.11.081
  31. Zhao X, Jia Y, Chen H, Yao H and Guo W (2019) Plasma-derived exosomal miR-183 associates with protein kinase activity and may serve as a novel predictive biomarker of myocardial ischemic injury. Exp Ther Med 18, 179-187
  32. Feng Y, Hang W, Sang Z et al (2019) Identification of exosomal and nonexosomal microRNAs associated with the drug resistance of ovarian cancer. Mol Med Rep 19, 3376-3392