Cited by 34MicroRNA in disease regulationLipid metabolism and disordersLipid metabolism and biosynthesis

MicroRNA-124 Regulates Fatty Acid and Triglyceride Homeostasis

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Shaw, Tyler A., Singaravelu, Ragunath, Powdrill, Megan H., Nhan, Jordan, Ahmed, Nadine, Özcelik, Dennis, Pezacki, John Paul·2018·iScience

Abstract

MicroRNAs (miRNAs) are part of a complex regulatory network that modulates cellular lipid metabolism. Here, we identify miR-124 as a regulator of triglyceride (TG) metabolism. This study advances our knowledge of the role of miR-124 in human hepatoma cells. Transcriptional profiling of Huh7.5 cells overexpressing miR-124 reveals enrichment for host factors involved in fatty acid oxidation among repressed miRNA targets. In addition, miR-124 down-regulates arylacetamide deacetylase (AADAC) and adipose triglyceride lipase, lipases proposed to mediate breakdown of hepatic TG stores for lipoprotein assembly and mitochondrial β-oxidation. Consistent with the inhibition of TG and fatty acid catabolism, miR-124 expression promotes cellular TG accumulation. Interestingly, miR-124 inhibits the production of hepatitis C virus, a virus that hijacks lipid pathways during its life cycle. Antiviral activity of miR-124 is consistent with repression of AADAC, a pro-viral host factor. Overall, our data highlight miR-124 as a novel regulator of TG metabolism in human hepatoma cells.

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Crossref · 10.1016/j.isci.2018.11.028

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  • Such mechanisms may not be microglia-specific because miR-124 has been shown to increase fatty acid and triglyceride content in liver cells.

    “However, such mechanisms may not be microglia-specific due to the fact that miR-124 has been shown to increase fatty acid and triglyceride content in liver cells [66, 67].”

    From HIV-TAT dysregulates microglial lipid metabolism through SREBP2/miR-124 axis: Implication of lipid droplet accumulation microglia in NeuroHIV (2025) · cites this paper as [66]

    The Results section, “miR-124 Promotes Cellular TG Accumulation” (page not provided), reports significantly increased triglyceride content in miR-124-treated Huh7.5 liver cells. It discusses free fatty acid accumulation as a rationale but does not report measuring an increase in fatty acid content, so that part of the claim is not established. (LLM, conf=0.87)

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Research works printed but not linked: 41

  1. Agarwal V. Bell G.W. Nam J.-W. Bartel D.P. Predicting effective microRNA target sites in mammalian mRNAs Elife 4 2015 e05005 PMC4532895 26267216
  2. Ben-Hamo R. Efroni S. MicroRNA regulation of molecular pathways as a generic mechanism and as a core disease phenotype Oncotarget 6 2015 1594 1604 25593195 PMC4359317
  3. Bonci D. Coppola V. Musumeci M. Addario A. Giuffrida R. Memeo L. D’Urso L. Pagliuca A. Biffoni M. Labbaye C. The miR-15a-miR-16-1 cluster controls prostate cancer by targeting multiple oncogenic activities Nat. Med. 14 2008 1271 1277 18931683
  4. Chen J. Bardes E.E. Aronow B.J. Jegga A.G. ToppGene Suite for gene list enrichment analysis and candidate gene prioritization Nucleic Acids Res. 37 2009 W305 W311 19465376 PMC2703978
  5. Chi S.W. Zang J.B. Mele A. Darnell R.B. Argonaute HITS-CLIP decodes microRNA-mRNA interaction maps Nature 460 2009 479 486 19536157 PMC2733940
  6. Chukkapalli V. Heaton N.S. Randall G. Lipids at the interface of virus-host interactions Curr. Opin. Microbiol. 15 2012 512 518 22682978 PMC3424344
  7. Das S.K. Stadelmeyer E. Schauer S. Schwarz A. Strohmaier H. Claudel T. Zechner R. Hoefler G. Vesely P.W. MicroRNA-124a regulates lipolysis via adipose triglyceride lipase and comparative gene identification 58 Int. J. Mol. Sci. 16 2015 8555 8568 25894224 PMC4425096
  8. Elmén J. Lindow M. Silahtaroglu A. Bak M. Christensen M. Lind-Thomsen A. Hedtjärn M. Hansen J.B. Hansen H.F. Straarup E.M. Antagonism of microRNA-122 in mice by systemically administered LNA-antimiR leads to up-regulation of a large set of predicted target mRNAs in the liver Nucleic Acids Res. 36 2008 1153 1162 18158304 PMC2275095
  9. Esau C. Davis S. Murray S.F. Yu X.X. Pandey S.K. Pear M. Watts L. Booten S.L. Graham M. McKay R. miR-122 regulation of lipid metabolism revealed by in vivo antisense targeting Cell Metab. 3 2006 87 98 16459310
  10. Gu S. Jin L. Zhang F. Sarnow P. Kay M.A. Biological basis for restriction of microRNA targets to the 3' untranslated region in mammalian mRNAs Nat. Struct. Mol. Biol. 16 2009 144 150 19182800 PMC2713750
  11. Hashimoto Y. Akiyama Y. Yuasa Y. Multiple-to-multiple relationships between MicroRNAs and target genes in gastric cancer PLoS One 8 2013 e62589 23667495 PMC3648557
  12. Houten S.M. Wanders R.J. A general introduction to the biochemistry of mitochondrial fatty acid beta-oxidation J. Inherit. Metab. Dis. 33 2010 469 477 20195903 PMC2950079
  13. Jopling C.L. Yi M. Lancaster A.M. Lemon S.M. Sarnow P. Modulation of hepatitis C virus RNA abundance by a liver-specific MicroRNA Science 1 2005 1577 1581 16141076
  14. Karginov F.V. Conaco C. Xuan Z. Schmidt B.H. Parker J.S. Mandel G. Hannon G.J. A biochemical approach to identifying microRNA targets Proc. Natl. Acad. Sci. U S A 104 2007 19291 19296 18042700 PMC2148283
  15. Kersten S. Seydoux J. Peters J.M. Gonzalez F.J. Desvergne B. Wahli W. Peroxisome proliferator-activated receptor alpha mediates the adaptive response to fasting J. Clin. Invest. 103 1999 1489 1498 10359558 PMC408372
  16. Krützfeldt J. Rajewsky N. Braich R. Rajeev K.G. Tuschl T. Manoharan M. Stoffel M. Silencing of microRNAs in vivo with ‘antagomirs’ Nature 438 2005 685 689 16258535
  17. Li Q. Lowey B. Sodroski C. Krishnamurthy S. Alao H. Cha H. Chiu S. El-Diwany R. Ghany M.G. Liang T.J. Cellular microRNA networks regulate host dependency of hepatitis C virus infection Nat. Commun. 8 2017 1789 29176620 PMC5702611
  18. Lo V. Erickson B. Thomason-Hughes M. Ko K.W. Dolinsky V.W. Nelson R. Lehner R. Arylacetamide deacetylase attenuates fatty-acid-induced triacylglycerol accumulation in rat hepatoma cells J. Lipid Res. 51 2010 368 377 19654421 PMC2803239
  19. Mashek D.G. Hepatic fatty acid trafficking: multiple forks in the road Adv. Nutr. 4 2013 697 710 24228201 PMC3823518
  20. McCaskill J.L. Ressel S. Alber A. Redford J. Power U.F. Schwarze J. Dutia B.M. Buck A.H. Broad-spectrum inhibition of respiratory virus infection by microRNA mimics targeting p38 MAPK signaling Mol. Ther. Nucleic Acids 7 2017 256 266 28624201 PMC5415959
  21. Moore K.J. Rayner K.J. Suárez Y. Fernández-Hernando C. The role of microRNAs in cholesterol efflux and hepatic lipid metabolism Ann. Rev. Nutr. 31 2011 49 63 21548778 PMC3612434
  22. Ning B.F. Ding J. Liu J. Yin C. Xu W.-P. Cong W.-M. Zhang Q. Chen F. Han T. Deng X. Hepatocyte nuclear factor 4α-nuclear factor-κB feedback circuit modulates liver cancer progression Hepatology 60 2014 1607 1619 24752868
  23. Nourbakhsh M. Douglas D.N. Pu C.H. Lewis J.T. Kawahara T. Lisboa L.F. Wei E. Asthana S. Quiroga A.D. Law L.M. Arylacetamide deacetylase: a novel host factor with important roles in the lipolysis of cellular triacylglycerol stores, VLDL assembly and HCV production J. Hepatol. 59 2013 336 343 23542347
  24. Ong K.T. Mashek M.T. Bu S.Y. Greenberg A.S. Mashek D.G. Adipose triglyceride lipase is a major hepatic lipase that regulates triacylglycerol turnover and fatty acid signaling and partitioning Hepatology 53 2011 116 126 20967758 PMC3025059
  25. Park H.S. Jang J.E. Ko M.S. Woo S.H. Kim B.J. Kim H.S. Park H.S. Park I.S. Koh E.H. Lee K.U. Statins increase mitochondrial and peroxisomal fatty acid oxidation in the liver and prevent non-alcoholic steatohepatitis in mice Diabetes Metab. J. 40 2016 376 385 27098507 PMC5069394
  26. Pasquinelli A.E. MicroRNAs and their targets: recognition, regulation and an emerging reciprocal relationship Nat. Rev. Genet. 13 2012 271 282 22411466
  27. Phulukdaree A. Moodley D. Khan S. Chuturgoon A.A. Atorvastatin increases miR-124a expression: a mechanism of Gamt modulation in liver cells J. Cell. Biochem. 116 2015 2620 2627 25926069
  28. Rakhshandehroo M. Knoch B. Muller M. Kersten S. Peroxisome proliferator-activated receptor alpha target genes PPAR Res. 2010 2010 612089 20936127 PMC2948931
  29. Ress C. Kaser S. Mechanisms of intrahepatic triglyceride accumulation World J. Gastroenterol. 22 2016 1664 1673 26819531 PMC4721997
  30. Ross M.K. Borazjani A. Wang R. Crow J.A. Xie S. Examination of the carboxylesterase phenotype in human liver Arch. Biochem. Biophys. 522 2012 44 56 22525521 PMC3569858
  31. Russell R.S. Meunier J.C. Takikawa S. Faulk K. Engle R.E. Bukh J. Purcell R.H. Emerson S.U. Advantages of a single-cycle production assay to study cell culture-adaptive mutations of hepatitis C virus Proc. Natl. Acad. Sci. U S A 105 2008 4370 4375 18334634 PMC2393785
  32. Santhakumar D. Forster T. Laqtom N.N. Fragkoudis R. Dickinson P. Abreu-Goodger C. Manakov S.A. Choudhury N.R. Griffiths S.J. Vermeulen A. Combined agonist-antagonist genome-wide functional screening identifies broadly active antiviral microRNAs Proc. Natl. Acad. Sci. U S A 107 2010 13830 13835 20643939 PMC2922253
  33. Shirasaki T. Honda M. Shimakami T. Horii R. Yamashita T. Sakai Y. Sakai A. Okada H. Watanabe R. Murakami S. MicroRNA-27a regulates lipid metabolism and inhibits hepatitis C virus replication in human hepatoma cells J. Virol. 87 2013 5270 5286 23449803 PMC3624309
  34. Singaravelu R. Chen R. Lyn R.K. Jones D.M. O'Hara S. Rouleau Y. Cheng J. Srinivasan P. Nasheri N. Russell R.S. Hepatitis C virus induced up-regulation of microRNA-27: a novel mechanism for hepatic steatosis Hepatology 59 2014 98 108 23897856
  35. Singaravelu R. O'Hara S. Jones D.M. Chen R. Taylor N.G. Srinivasan P. Quan C. Roy D.G. Steenbergen R.H. Kumar A. MicroRNAs regulate the immunometabolic response to viral infection in the liver Nat. Chem. Biol. 11 2015 988 993 26479438
  36. Singaravelu R. Quan C. Powdrill M.H. Shaw T.A. Srinivasan P. Lyn R.K. Alonzi R.C. Jones D.M. Filip R. Russell R.S. MicroRNA-7 mediates cross-talk between metabolic signaling pathways in the liver Sci. Rep. 8 2018 361 29321595 PMC5762714
  37. Singaravelu R. Srinivasan P. Pezacki J.P. Armand-Frappier Outstanding Student Award — the emerging role of 25-hydroxycholesterol in innate immunity Can. J. Microbiol. 61 2015 521 530 26182401
  38. Strijbis K. Vaz F.M. Distel B. Enzymology of the carnitine biosynthesis pathway IUBMB Life 62 2010 357 362 20306513
  39. Valentino A. Calarco A. Di Salle A. Finicelli M. Crispi S. Calogero R.A. Riccardo F. Sciarra A. Gentilucci A. Galderisi U. Deregulation of MicroRNAs mediated control of carnitine cycle in prostate cancer: molecular basis and pathophysiological consequences Oncogene 36 2017 6030 6040 28671672
  40. Vallianou I. Dafou D. Vassilaki N. Mavromara P. Hadzopoulou-Cladaras M. Hepatitis C virus suppresses Hepatocyte Nuclear Factor 4 alpha, a key regulator of hepatocellular carcinoma Int. J. Biochem. Cell Biol. 78 2016 315 326 27477312
  41. Xu J. Li Y. Chen W.D. Xu Y. Yin L. Ge X. Jadhav K. Adorini L. Zhang Y. Hepatic carboxylesterase 1 is essential for both normal and farnesoid X receptor-controlled lipid homeostasis Hepatology 59 2014 1761 1771 24038130 PMC3938573

Cited by

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Authors
Shaw, T. A., Singaravelu, R., Powdrill, M. H., Nhan, J., Ahmed, N., Özcelik, D., & Pezacki, J. P.
Affiliations
University of Ottawa (CA)
Corresponding author
Pezacki, John Paul
Venue
iScience
Publisher
Elsevier BV
Published
2018-12
Volume
10
Pages
149-157
ISSN
2589-0042 (ISSN-L)
OpenAlex
W2901951586
Cited by
34
References
4
Citations by year
2026: 2 · 2025: 6 · 2024: 4 · 2023: 2 · 2022: 7 · 2021: 3 · 2020: 8 · 2019: 2
FWCI
0.98
Type
journal article
Language
en
Open access
Locations
  • iScience (publishedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • Canadian Institutes of Health Research
  • Natural Sciences and Engineering Research Council of Canada
  • Canadian Network
  • Life Science Research Foundation
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
Keywords
miR-124, triglyceride metabolism, fatty acid homeostasis, arylacetamide deacetylase, adipose triglyceride lipase, fatty acid oxidation, hepatitis C virus, antiviral activity, host factors, lipid metabolism, triglyceride accumulation

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