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Long noncoding RNAs in the metabolic control of inflammation and immune disorders

Cellular & Molecular Immunology volume 16, pages 1–5 (2019)Cite this article

Abstract

The metabolic control of immune cell development and function has been shown to be critical for the maintenance of immune homeostasis and is also involved in the pathogenesis of immune disorders. Pathogenic infections or cancers may induce metabolic reprogramming through different pathways to meet the energy and metabolite demands for pathogen propagation or cancer progression. In addition, some deregulated metabolites could trigger or regulate immune responses, thus causing chronic inflammation or immune disorders, such as viral infection, cancer and obesity. Therefore, the methods through which metabolism is regulated and the role of metabolic regulation in inflammation and immunity attract much attention. Epigenetic regulation of inflammation and immunity is an emerging field. Long noncoding RNAs (lncRNAs) have been well documented to play crucial roles in many biological processes through diverse mechanisms, including immune regulation and metabolic alternation. Here, we review the functions and mechanisms of lncRNAs in the metabolic regulation of inflammatory immune disorders, aiming to deepen our understanding of the epigenetic regulation of inflammation and immunity.

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Fig. 1: lncRNAs mediate the metabolic regulation of inflammation and immune disorders by targeting different metabolic pathways.

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References

  1. Redis, R. S. & Calin, G. A. SnapShot: non-coding RNAs and Metabolism. Cell Metab. 25, 220–220 (2017). e221.

    Article  CAS  Google Scholar 

  2. Zhang, X., Liu, J. & Cao, X. Metabolic control of T-cell immunity via epigenetic mechanisms. Cell Mol. Immunol. 15, 203–205 (2018).

    Article  Google Scholar 

  3. Lu, Y. et al. Glucocorticoid receptor promotes the function of myeloid-derived suppressor cells by suppressing HIF1alpha-dependent glycolysis. Cell Mol. Immunol. (2017) [Epub ahead of print].

  4. Pearce, E. L. & Pearce, E. J. Metabolic pathways in immune cell activation and quiescence. Immunity 38, 633–643 (2013).

    Article  CAS  Google Scholar 

  5. McKinney, E. F. & Smith, K. G. C. Metabolic exhaustion in infection, cancer and autoimmunity. Nat. Immunol. 19, 213–221 (2018).

    Article  CAS  Google Scholar 

  6. Hotamisligil, G. S. Inflammation and metabolic disorders. Nature 444, 860–867 (2006).

    Article  CAS  Google Scholar 

  7. Cairns, R. A., Harris, I. S. & Mak, T. W. Regulation of cancer cell metabolism. Nat. Rev. Cancer 11, 85–95 (2011).

    Article  CAS  Google Scholar 

  8. Atianand, M. K. et al. A long noncoding RNA lincRNA-EPS acts as a transcriptional brake to restrain inflammation. Cell 165, 1672–1685 (2016).

    Article  CAS  Google Scholar 

  9. Guo, C. J., Zhang, W. & Gershwin, M. E. Long noncoding RNA lncKdm2b: a critical player in the maintenance of group 3 innate lymphoid cells. Cell. Mol. Immunol. 15, 5–7 (2018).

    Article  CAS  Google Scholar 

  10. Wang, P. et al. The STAT3-binding long noncoding RNA lnc-DC controls human dendritic cell differentiation. Science 344, 310–313 (2014).

    Article  CAS  Google Scholar 

  11. Mazzon, M., Castro, C., Roberts, L. D., Griffin, J. L. & Smith, G. L. A role for vaccinia virus protein C16 in reprogramming cellular energy metabolism. J. Gen. Virol. 96, 395–407 (2015).

    Article  CAS  Google Scholar 

  12. Fontaine, K. A., Camarda, R. & Lagunoff, M. Vaccinia virus requires glutamine but not glucose for efficient replication. J. Virol. 88, 4366–4374 (2014).

    Article  Google Scholar 

  13. Thai, M. et al. MYC-induced reprogramming of glutamine catabolism supports optimal virus replication. Nat. Commun. 6, 8873 (2015).

    Article  CAS  Google Scholar 

  14. Fontaine, K. A., Sanchez, E. L., Camarda, R. & Lagunoff, M. Dengue virus induces and requires glycolysis for optimal replication. J. Virol. 89, 2358–2366 (2015).

    Article  Google Scholar 

  15. Ripoli, M. et al. Hepatitis C virus-linked mitochondrial dysfunction promotes hypoxia-inducible factor 1 alpha-mediated glycolytic adaptation. J. Virol. 84, 647–660 (2010).

    Article  CAS  Google Scholar 

  16. Thai, M. et al. Adenovirus E4ORF1-induced MYC activation promotes host cell anabolic glucose metabolism and virus replication. Cell Metab. 19, 694–701 (2014).

    Article  CAS  Google Scholar 

  17. Vastag, L., Koyuncu, E., Grady, S. L., Shenk, T. E. & Rabinowitz, J. D. Divergent effects of human cytomegalovirus and herpes simplex virus-1 on cellular metabolism. PLoS Pathog. 7, e1002124 (2011).

    Article  CAS  Google Scholar 

  18. Mazzon, M. et al. Alphavirus-induced hyperactivation of PI3K/AKT directs pro-viral metabolic changes. PLoS Pathog. 14, e1006835 (2018).

    Article  Google Scholar 

  19. Wang, P. & Xu, J. An interferon-independent lncRNA promotes viral replication by modulating cellular metabolism. Science 358, 1051–1055 (2017).

    Article  CAS  Google Scholar 

  20. Perlemuter, G. et al. Hepatitis C virus core protein inhibits microsomal triglyceride transfer protein activity and very low density lipoprotein secretion: a model of viral-related steatosis. FASEB J. 16, 185–194 (2002).

    Article  CAS  Google Scholar 

  21. Li, Z. Q. et al. Hepatitis C virus core protein impairs metabolic disorder of liver cell via HOTAIR-Sirt1 signalling. Biosci. Rep. 36, e00336 (2016).

  22. Jiang, M. & Zhang, S. et al. Self-recognition of an inducible host lncRNA by RIG-I feedback restricts innate immune response. Cell 173, 906–919 (2018).

    Article  CAS  Google Scholar 

  23. Sorini, C., Cosorich, I. & Falcone, M. New therapeutic perspectives in Type 1 Diabetes: dietary interventions prevent beta cell-autoimmunity by modifying the gut metabolic environment. Cell. Mol. Immunol. 14, 951–953 (2017).

    Article  CAS  Google Scholar 

  24. Losko, M., Kotlinowski, J. & Jura, J. Long noncoding RNAs in metabolic syndrome related disorders. Mediat. Inflamm. 2016, 5365209 (2016).

    Article  Google Scholar 

  25. Marchesini, G. et al. Nonalcoholic fatty liver disease: a feature of the metabolic syndrome. Diabetes 50, 1844–1850 (2001).

    Article  CAS  Google Scholar 

  26. Cai, R. et al. Adiponectin AS lncRNA inhibits adipogenesis by transferring from nucleus to cytoplasm and attenuating Adiponectin mRNA translation. Biochim. Biophys. Acta 1863, 420–432 (2018).

    Article  CAS  Google Scholar 

  27. Zhang, Y. et al. Bcl2 is a critical regulator of bile acid homeostasis by dictating Shp and lncRNA H19 function. Sci. Rep. 6, 20559 (2016).

    Article  CAS  Google Scholar 

  28. Liu, C. et al. lncRNA H19 interacts with polypyrimidine tract-binding protein 1 to reprogram hepatic lipid homeostasis. Hepatology 67, 1768–1783 (2018).

    Article  CAS  Google Scholar 

  29. Rotman, Y. & Sanyal, A. J. Current and upcoming pharmacotherapy for non-alcoholic fatty liver disease. Gut 66, 180–190 (2017).

    Article  CAS  Google Scholar 

  30. Cui, X. et al. A transcribed ultraconserved noncoding RNA, uc.417, serves as a negative regulator of brown adipose tissue thermogenesis. FASEB J. 30, 4301–4312 (2016).

    Article  CAS  Google Scholar 

  31. Kahn, S. E., Hull, R. L. & Utzschneider, K. M. Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature 444, 840–846 (2006).

    Article  CAS  Google Scholar 

  32. Goyal, N., Kesharwani, D. & Datta, M. Lnc-ing non-coding RNAs with metabolism and diabetes: Roles of lncRNAs. Cell Mol. Life Sci. 75, 1827–1837 (2018).

    Article  CAS  Google Scholar 

  33. Gao, Y. et al. The H19/let-7 double-negative feedback loop contributes to glucose metabolism in muscle cells. Nucleic Acids Res. 42, 13799–13811 (2014).

    Article  CAS  Google Scholar 

  34. Arnes, L., Akerman, I., Balderes, D. A., Ferrer, J. & Sussel, L. βlinc1 encodes a long noncoding RNA that regulates islet β-cell formation and function. Genes Dev. 30, 502–507 (2016).

    Article  CAS  Google Scholar 

  35. Wang, W. et al. Mitochondrial fission triggered by hyperglycemia is mediated by ROCK1 activation in podocytes and endothelial cells. Cell Metab. 15, 186–200 (2012).

    Article  CAS  Google Scholar 

  36. Guo, K. et al. Protective role of PGC-1αin diabetic nephropathy is associated with the inhibition of ROS through mitochondrial dynamic remodeling. PLoS ONE 10, e0125176 (2015).

    Article  Google Scholar 

  37. Long, J. et al. Long noncoding RNA Tug1 regulates mitochondrial bioenergetics in diabetic nephropathy. J. Clin. Invest. 126, 4205–4218 (2016).

    Article  Google Scholar 

  38. Leucci, E. et al. Melanoma addiction to the long non-coding RNA SAMMSON. Nature 531, 518–522 (2016).

    Article  CAS  Google Scholar 

  39. Fogal, V. et al. Mitochondrial p32 protein is a critical regulator of tumor metabolism via maintenance of oxidative phosphorylation. Mol. Cell Biol. 30, 1303–1318 (2010).

    Article  CAS  Google Scholar 

  40. Yagi, M. et al. p32/gC1qR is indispensable for fetal development and mitochondrial translation: importance of its RNA-binding ability. Nucleic Acids Res. 40, 9717–9737 (2012).

    Article  CAS  Google Scholar 

  41. Muta, T., Kang, D., Kitajima, S., Fujiwara, T. & Hamasaki, N. p32 protein, a splicing factor 2-associated protein, is localized in mitochondrial matrix and is functionally important in maintaining oxidative phosphorylation. J. Biol. Chem. 272, 24363–24370 (1997).

    Article  CAS  Google Scholar 

  42. Hardie, D. G., Schaffer, B. E. & Brunet, A. AMPK: An energy-sensing pathway with multiple inputs and outputs. Trends Cell Biol. 26, 190–201 (2016).

    Article  CAS  Google Scholar 

  43. Shackelford, D. B. & Shaw, R. J. The LKB1-AMPK pathway: metabolism and growth control in tumour suppression. Nat. Rev. Cancer 9, 563–575 (2009).

    Article  CAS  Google Scholar 

  44. Liu, X. et al. LncRNA NBR2 engages a metabolic checkpoint by regulating AMPK under energy stress. Nat. Cell Biol. 18, 431–442 (2016).

    Article  CAS  Google Scholar 

  45. Tomlinson, I. et al. A genome-wide association scan of tag SNPs identifies a susceptibility variant for colorectal cancer at 8q24.21. Nat. Genet. 39, 984–988 (2007).

    Article  CAS  Google Scholar 

  46. Tuupanen, S. et al. The common colorectal cancer predisposition SNP rs6983267 at chromosome 8q24 confers potential to enhanced Wnt signaling. Nat. Genet. 41, 885–890 (2009).

    Article  CAS  Google Scholar 

  47. Redis, R. S. et al. Allele-specific reprogramming of cancer metabolism by the Long non-coding RNA CCAT2. Mol. Cell 61, 640 (2016).

    Article  CAS  Google Scholar 

  48. Xiao, Z. D. et al. Energy stress-induced lncRNA FILNC1 represses c-Myc-mediated energy metabolism and inhibits renal tumor development. Nat. Commun. 8, 783 (2017).

    Article  Google Scholar 

  49. Hung, C.-L. et al. A long noncoding RNA connects c-Myc to tumor metabolism. Proc. Natl. Acad. Sci. USA 111, 18697–18702 (2014).

    Article  CAS  Google Scholar 

  50. Xiang, S. et al. LncRNA IDH1-AS1 links the functions of c-Myc and HIF1α via IDH1 to regulate the Warburg effect. Proc. Natl. Acad. Sci. USA 115, E1465–E1474 (2018).

    Article  CAS  Google Scholar 

  51. Yang, B. et al. Overexpression of lncRNA IGFBP4-1 reprograms energy metabolism to promote lung cancer progression. Mol. Cancer 16, 154 (2017).

    Article  Google Scholar 

  52. Cui, X. et al. The long non-coding RNA Gm10768 activates hepatic gluconeogenesis by sequestering microRNA-214 in mice. J. Biol. Chem. 293, 4097–4109 (2018).

    Article  CAS  Google Scholar 

  53. Zgheib, C., Hodges, M. M., Hu, J., Liechty, K. W. & Xu, J. Long non-coding RNA Lethe regulates hyperglycemia-induced reactive oxygen species production in macrophages. PLoS ONE 12, e0177453 (2017).

    Article  Google Scholar 

  54. Sallam, T., Jones, M. & Thomas, B. J. et al. Transcriptional regulation of macrophage cholesterol efflux and atherogenesis by a long noncoding RNA. Nat. Med. 24, 304–312 (2018).

    Article  CAS  Google Scholar 

  55. Li, H. J. et al. LncRNA UCA1 promotes mitochondrial function of bladder cancer via the MiR-195/ARL2 signaling pathway. Cell. Physiol. Biochem. 43, 2548–2561 (2017).

    Article  CAS  Google Scholar 

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Acknowledgements

This work was supported by grants from the National Natural Science Foundation of China (81788101, 91542000) and CAMS Innovation Fund for Medical Science (2016-I2M-1-003).

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Authors and Affiliations

  1. Institute of Immunology, Zhejiang University School of Medicine, Hangzhou, 310058, China

    Junfang Xu & Xuetao Cao

  2. Department of Immunology & Center for Immunotherapy, Institute of Basic Medical Sciences, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100005, China

    Xuetao Cao

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Correspondence to Xuetao Cao.

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Xu, J., Cao, X. Long noncoding RNAs in the metabolic control of inflammation and immune disorders. Cell Mol Immunol 16, 1–5 (2019). https://doi.org/10.1038/s41423-018-0042-y

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