Differential Expression of Glucocorticoid Receptor Noncoding RNA Repressor Gas5 in Autoimmune and Inflammatory Diseases

T. Mayama; A. K. Marr; T. Kino

doi:10.1055/s-0042-106898

Hormone and Metabolic Research, Inhaltsverzeichnis

Horm Metab Res 2016; 48(08): 550-557
DOI: 10.1055/s-0042-106898

Endocrine Research

Differential Expression of Glucocorticoid Receptor Noncoding RNA Repressor Gas5 in Autoimmune and Inflammatory Diseases

T. Mayama

¹Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, USA

²Present address: Department of Integrate Bioscience, Graduate School of Medical and Pharmaceutical Sciences, Chiba University, Chiba, Japan

,

A. K. Marr

³Division of Genetics, Sidra Medical and Research Center, Doha, Qatar

,

T. Kino

¹Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, USA

³Division of Genetics, Sidra Medical and Research Center, Doha, Qatar

› Institutsangaben

Abstract

Glucocorticoids have strong regulatory actions on the immune system and act as potent therapeutic compounds for autoimmune and inflammatory diseases. We previously reported that the long noncoding RNA growth arrest-specific 5 (Gas5), which accumulates inside the cells in response to cellular starvation/growth arrest, functions as a potent repressor of the glucocorticoid receptor (GR) through its RNA “glucocorticoid response element (GRE)”. To evaluate potential roles of Gas5 in immune-related disorders, we examined Gas5 RNA levels in various autoimmune, inflammatory, and infectious diseases using the microarray data available in the Gene Expression Omnibus. We found that Gas5 levels were altered in whole blood or leukocytes of the patients with rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, and sarcoidosis. Gas5 levels were also altered in infectious diseases, such as by the human immunodeficiency virus type-1 and influenza virus, and bacterial sepsis. In our experimental analysis using mice, Gas5 levels were kept at high basal levels and did not respond to fasting in immune organs, such as spleen and thymus, while its levels in metabolic organs, including liver, fat, and skeletal muscles, were low at baseline and were highly elevated upon this treatment, possibly through suppression of the mTOR pathway. These results suggest that Gas5 plays a role in the regulation of immune functions and pathogenesis/pathophysiology of autoimmune, inflammatory, and infectious diseases in part through modulation of the GR transcriptional activity via its decoy RNA “GRE”. Changes in the Gas5 levels may also influence disease response to immunosuppressive glucocorticoid therapy.

Key words

autoimmune diseases - fasting - glucocorticoids - mammalian target of rapamycin (mTOR) - tissue glucocorticoid sensitivity

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References
1 Kino T. Glucocorticoid receptor. In: Adrenal Disease and Function. De Groot LJ, Beck-Peccoz P, Chrousos GP, Dungan K, Grossman A, Hershman JM, Koch C, McLachlan R, New M, Rebar R, Singer F, Vinik A, Weickert MO. (eds.) South Dartmouth, MA: Endotext.org; 2000
2 Chrousos GP. Stress and disorders of the stress system. Nat Rev Endocrinol 2009; 5: 374-381
3 Kino T, Charmandari E, Chrousos GP. Basic and clinical implications of glucocorticoid action–focus on development. National Institutes of Health, Bethesda, Maryland, USA. June 17-18, 2003. Introduction and abstracts. Horm Metab Res 2003; 35: 628-648
4 Kino T, Chrousos GP. Glucocorticoid effect on gene expression. In: Steckler T, Kalin NH, Reul JMHM. eds Handbook on Stress and the Brain Part 1. Amsterdam: Elsevier BV; 2004: 295-312
5 Thompson EB. Stepping stones in the path of glucocorticoid-driven apoptosis of lymphoid cells. Acta Biochim Biophys Sin (Shanghai) 2008; 40: 595-600
6 Ekman B, Alstrand N, Bachrach-Lindstrom M, Jenmalm MC, Wahlberg J. Altered chemokine Th1/Th2 balance in Addison’s disease: relationship with hydrocortisone dosing and quality of life. Horm Metab Res 2014; 46: 48-53
7 Inaba H, Pui CH. Glucocorticoid use in acute lymphoblastic leukaemia. Lancet Oncol 2010; 11: 1096-1106
8 Chrousos GP, Kino T. Intracellular glucocorticoid signaling: a formerly simple system turns stochastic. Sci STKE 2005; 2005: pe48
9 Carninci P, Kasukawa T, Katayama S, Gough J, Frith MC, Maeda N, Oyama R, Ravasi T, Lenhard B, Wells C, Kodzius R, Shimokawa K, Bajic VB, Brenner SE, Batalov S, Forrest AR, Zavolan M, Davis MJ, Wilming LG, Aidinis V, Allen JE, Ambesi-Impiombato A, Apweiler R, Aturaliya RN, Bailey TL, Bansal M, Baxter L, Beisel KW, Bersano T, Bono H, Chalk AM, Chiu KP, Choudhary V, Christoffels A, Clutterbuck DR, Crowe ML, Dalla E, Dalrymple BP, de Bono B, Della Gatta G, di Bernardo D, Down T, Engstrom P, Fagiolini M, Faulkner G, Fletcher CF, Fukushima T, Furuno M, Futaki S, Gariboldi M, Georgii-Hemming P, Gingeras TR, Gojobori T, Green RE, Gustincich S, Harbers M, Hayashi Y, Hensch TK, Hirokawa N, Hill D, Huminiecki L, Iacono M, Ikeo K, Iwama A, Ishikawa T, Jakt M, Kanapin A, Katoh M, Kawasawa Y, Kelso J, Kitamura H, Kitano H, Kollias G, Krishnan SP, Kruger A, Kummerfeld SK, Kurochkin IV, Lareau LF, Lazarevic D, Lipovich L, Liu J, Liuni S, McWilliam S, Madan Babu M, Madera M, Marchionni L, Matsuda H, Matsuzawa S, Miki H, Mignone F, Miyake S, Morris K, Mottagui-Tabar S, Mulder N, Nakano N, Nakauchi H, Ng P, Nilsson R, Nishiguchi S, Nishikawa S, Nori F, Ohara O, Okazaki Y, Orlando V, Pang KC, Pavan WJ, Pavesi G, Pesole G, Petrovsky N, Piazza S, Reed J, Reid JF, Ring BZ, Ringwald M, Rost B, Ruan Y, Salzberg SL, Sandelin A, Schneider C, Schonbach C, Sekiguchi K, Semple CA, Seno S, Sessa L, Sheng Y, Shibata Y, Shimada H, Shimada K, Silva D, Sinclair B, Sperling S, Stupka E, Sugiura K, Sultana R, Takenaka Y, Taki K, Tammoja K, Tan SL, Tang S, Taylor MS, Tegner J, Teichmann SA, Ueda HR, van Nimwegen E, Verardo R, Wei CL, Yagi K, Yamanishi H, Zabarovsky E, Zhu S, Zimmer A, Hide W, Bult C, Grimmond SM, Teasdale RD, Liu ET, Brusic V, Quackenbush J, Wahlestedt C, Mattick JS, Hume DA, Kai C, Sasaki D, Tomaru Y, Fukuda S, Kanamori-Katayama M, Suzuki M, Aoki J, Arakawa T, Iida J, Imamura K, Itoh M, Kato T, Kawaji H, Kawagashira N, Kawashima T, Kojima M, Kondo S, Konno H, Nakano K, Ninomiya N, Nishio T, Okada M, Plessy C, Shibata K, Shiraki T, Suzuki S, Tagami M, Waki K, Watahiki A, Okamura-Oho Y, Suzuki H, Kawai J, Hayashizaki Y. The transcriptional landscape of the mammalian genome. Science 2005; 309: 1559-1563
10 Ulitsky I, Bartel DP. lincRNAs: genomics, evolution, and mechanisms. Cell 2013; 154: 26-46
11 Lewis BP, Burge CB, Bartel DP. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 2005; 120: 15-20
12 Schneider C, King RM, Philipson L. Genes specifically expressed at growth arrest of mammalian cells. Cell 1988; 54: 787-793
13 Smith CM, Steitz JA. Classification of gas5 as a multi-small-nucleolar-RNA (snoRNA) host gene and a member of the 5′-terminal oligopyrimidine gene family reveals common features of snoRNA host genes. Mol Cell Biol 1998; 18: 6897-6909
14 Amaldi F, Pierandrei-Amaldi P. TOP genes: a translationaly controlled class of genes including those coding for ribosomal proteins. In: Jeanteur P. ed Progress in molecular and subcellular biology. Berlin, Germany: Springer-Verlag; 1997: 1-17
15 Pickard MR, Williams GT. Molecular and cellular mechanisms of action of tumour suppressor GAS5 lncRNA. Genes (Basel) 2015; 6: 484-499
16 Liu Y, Zhao J, Zhang W, Gan J, Hu C, Huang G, Zhang Y. lncRNA GAS5 enhances G1 cell cycle arrest via binding to YBX1 to regulate p21 expression in stomach cancer. Sci Rep 2015; 5: 10159
17 Shi X, Sun M, Liu H, Yao Y, Kong R, Chen F, Song Y. A critical role for the long non-coding RNA GAS5 in proliferation and apoptosis in non-small-cell lung cancer. Mol Carcinog 2015; 54: E1-E12
18 Mourtada-Maarabouni M, Williams GT. Growth arrest on inhibition of nonsense-mediated decay is mediated by noncoding RNA GAS5. Biomed Res Int 2013; 358015
19 Tu ZQ, Li RJ, Mei JZ, Li XH. Down-regulation of long non-coding RNA GAS5 is associated with the prognosis of hepatocellular carcinoma. Int J Clin Exp Pathol 2014; 7: 4303-4309
20 Lu X, Fang Y, Wang Z, Xie J, Zhan Q, Deng X, Chen H, Jin J, Peng C, Li H, Shen B. Downregulation of gas5 increases pancreatic cancer cell proliferation by regulating CDK6. Cell Tissue Res 2013; 354: 891-896
21 Sun M, Jin FY, Xia R, Kong R, Li JH, Xu TP, Liu YW, Zhang EB, Liu XH, De W. Decreased expression of long noncoding RNA GAS5 indicates a poor prognosis and promotes cell proliferation in gastric cancer. BMC Cancer 2014; 14: 319
22 Yin D, He X, Zhang E, Kong R, De W, Zhang Z. Long noncoding RNA GAS5 affects cell proliferation and predicts a poor prognosis in patients with colorectal cancer. Med Oncol 2014; 31: 253
23 Cao S, Liu W, Li F, Zhao W, Qin C. Decreased expression of lncRNA GAS5 predicts a poor prognosis in cervical cancer. Int J Clin Exp Pathol 2014; 7: 6776-6783
24 Tao R, Hu S, Wang S, Zhou X, Zhang Q, Wang C, Zhao X, Zhou W, Zhang S, Li C, Zhao H, He Y, Zhu S, Xu J, Jiang Y, Li L, Gao Y. Association between indel polymorphism in the promoter region of lncRNA GAS5 and the risk of hepatocellular carcinoma. Carcinogenesis 2015; PMID 26163879
25 Kino T, Hurt DE, Ichijo T, Nader N, Chrousos GP, Noncoding RNA. gas5 is a growth arrest- and starvation-associated repressor of the glucocorticoid receptor. Sci Signal 2010; 3: ra8
26 Hudson WH, Pickard MR, de Vera IM, Kuiper EG, Mourtada-Maarabouni M, Conn GL, Kojetin DJ, Williams GT, Ortlund EA. Conserved sequence-specific lincRNA-steroid receptor interactions drive transcriptional repression and direct cell fate. Nat Commun 2014; 5: 5395
27 Papadopoulou A, Siamatras T, Delgado-Morales R, Amin ND, Shukla V, Zheng YL, Pant HC, Almeida OF, Kino T. Acute and chronic stress differentially regulate cyclin-dependent kinase 5 in mouse brain: implications to glucocorticoid actions and major depression. Transl Psychiatry 2015; 5: e578
28 Ng SS, Chang TH, Tailor P, Ozato K, Kino T. Virus-induced differential expression of nuclear receptors and coregulators in dendritic cells: implication to interferon production. FEBS Lett 2011; 585: 1331-1337
29 Kino T, Tiulpakov A, Ichijo T, Chheng L, Kozasa T, Chrousos GP. G protein b interacts with the glucocorticoid receptor and suppresses its transcriptional activity in the nucleus. J Cell Biol 2005; 169: 885-896
30 Nader N, Ng SS, Wang Y, Abel BS, Chrousos GP, Kino T. Liver x receptors regulate the transcriptional activity of the glucocorticoid receptor: implications for the carbohydrate metabolism. PLoS One 2012; 7: e26751
31 Hamilton TL, Stoneley M, Spriggs KA, Bushell M. TOPs and their regulation. Biochem Soc Trans 2006; 34: 12-16
32 Gandhi KS, McKay FC, Cox M, Riveros C, Armstrong N, Heard RN, Vucic S, Williams DW, Stankovich J, Brown M, Danoy P, Stewart GJ, Broadley S, Moscato P, Lechner-Scott J, Scott RJ, Booth DR. The multiple sclerosis whole blood mRNA transcriptome and genetic associations indicate dysregulation of specific T cell pathways in pathogenesis. Hum Mol Genet 2010; 19: 2134-2143
33 Katz SI. Classification, diagnosis, and differential diagnosis of multiple sclerosis. Curr Opin Neurol 2015; 28: 193-205
34 Risbano MG, Meadows CA, Coldren CD, Jenkins TJ, Edwards MG, Collier D, Huber W, Mack DG, Fontenot AP, Geraci MW, Bull TM. Altered immune phenotype in peripheral blood cells of patients with scleroderma-associated pulmonary hypertension. Clin Transl Sci 2010; 3: 210-218
35 Maertzdorf J, Weiner 3rd J, Mollenkopf HJ, Bauer T, Prasse A, Muller-Quernheim J, Kaufmann SH. Common patterns and disease-related signatures in tuberculosis and sarcoidosis. Proc Natl Acad Sci USA 2012; 109: 7853-7858
36 Koth LL, Solberg OD, Peng JC, Bhakta NR, Nguyen CP, Woodruff PG. Sarcoidosis blood transcriptome reflects lung inflammation and overlaps with tuberculosis. Am J Respir Crit Care Med 2011; 184: 1153-1163
37 Su R, Li MM, Bhakta NR, Solberg OD, Darnell EP, Ramstein J, Garudadri S, Ho M, Woodruff PG, Koth LL. Longitudinal analysis of sarcoidosis blood transcriptomic signatures and disease outcomes. Eur Respir J 2014; 44: 985-993
38 Wuyts W, Sterclova M, Vasakova M. Pitfalls in diagnosis and management of hypersensitivity pneumonitis. Curr Opin Pulm Med 2015; 21: 490-498
39 Sedaghat AR, German J, Teslovich TM, Cofrancesco Jr. J, Jie CC, Talbot Jr. CC, Siliciano RF. Chronic CD4+ T-cell activation and depletion in human immunodeficiency virus type 1 infection: type I interferon-mediated disruption of T-cell dynamics. J Virol 2008; 82: 1870-1883
40 Rotger M, Dang KK, Fellay J, Heinzen EL, Feng S, Descombes P, Shianna KV, Ge D, Gunthard HF, Goldstein DB, Telenti A. Genome-wide mRNA expression correlates of viral control in CD4+ T-cells from HIV-1-infected individuals. PLoS Pathog 2010; 6: e1000781
41 Kim SH, Gerver SM, Fidler S, Ward H. Adherence to antiretroviral therapy in adolescents living with HIV: systematic review and meta-analysis. AIDS 2014; 28: 1945-1956
42 Kino T. AIDS/HPA axis. In: Adrenal Disease and Function. De Groot LJ, Beck-Peccoz P, Chrousos G, Dungan K, Grossman A, Hershman JM, Koch C, McLachlan R, New M, Rebar R, Singer F, Vinik A, Weickert MO. (eds.) South Dartmouth, (MA): Endotext.org; 2000
43 Bermejo-Martin JF, Martin-Loeches I, Rello J, Anton A, Almansa R, Xu L, Lopez-Campos G, Pumarola T, Ran L, Ramirez P, Banner D, Ng DC, Socias L, Loza A, Andaluz D, Maravi E, Gomez-Sanchez MJ, Gordon M, Gallegos MC, Fernandez V, Aldunate S, Leon C, Merino P, Blanco J, Martin-Sanchez F, Rico L, Varillas D, Iglesias V, Marcos MA, Gandia F, Bobillo F, Nogueira B, Rojo S, Resino S, Castro C. Host adaptive immunity deficiency in severe pandemic influenza. Crit Care 2010; 14: R167
44 Franco LM, Bucasas KL, Wells JM, Nino D, Wang X, Zapata GE, Arden N, Renwick A, Yu P, Quarles JM, Bray MS, Couch RB, Belmont JW, Shaw CA. Integrative genomic analysis of the human immune response to influenza vaccination. Elife 2013; 2: e00299
45 Manceur AP, Kamen AA. Critical review of current and emerging quantification methods for the development of influenza vaccine candidates. Vaccine 2015; 33: 5913-5919
46 Sutherland A, Thomas M, Brandon RA, Brandon RB, Lipman J, Tang B, McLean A, Pascoe R, Price G, Nguyen T, Stone G, Venter D. Development and validation of a novel molecular biomarker diagnostic test for the early detection of sepsis. Crit Care 2011; 15: R149
47 Parnell GP, McLean AS, Booth DR, Armstrong NJ, Nalos M, Huang SJ, Manak J, Tang W, Tam OY, Chan S, Tang BM. A distinct influenza infection signature in the blood transcriptome of patients with severe community-acquired pneumonia. Crit Care 2012; 16: R157
48 Warren HS, Elson CM, Hayden DL, Schoenfeld DA, Cobb JP, Maier RV, Moldawer LL, Moore EE, Harbrecht BG, Pelak K, Cuschieri J, Herndon DN, Jeschke MG, Finnerty CC, Brownstein BH, Hennessy L, Mason PH, Tompkins RG. A genomic score prognostic of outcome in trauma patients. Mol Med 2009; 15: 220-227
49 Idaghdour Y, Quinlan J, Goulet JP, Berghout J, Gbeha E, Bruat V, de Malliard T, Grenier JC, Gomez S, Gros P, Rahimy MC, Sanni A, Awadalla P. Evidence for additive and interaction effects of host genotype and infection in malaria. Proc Natl Acad Sci U S A 2012; 109: 16786-16793
50 Hulsmans M, Geeraert B, De Keyzer D, Mertens A, Lannoo M, Vanaudenaerde B, Hoylaerts M, Benhabiles N, Tsatsanis C, Mathieu C, Holvoet P. Interleukin-1 receptor-associated kinase-3 is a key inhibitor of inflammation in obesity and metabolic syndrome. PLoS One 2012; 7: e30414
51 Magnuson B, Ekim B, Fingar DC. Regulation and function of ribosomal protein S6 kinase (S6K) within mTOR signalling networks. Biochem J 2012; 441: 1-21
52 Haywood ME, Rose SJ, Horswell S, Lees MJ, Fu G, Walport MJ, Morley BJ. Overlapping BXSB congenic intervals, in combination with microarray gene expression, reveal novel lupus candidate genes. Genes Immun 2006; 7: 250-263
53 Pickard MR, Mourtada-Maarabouni M, Williams GT. Long non-coding RNA GAS5 regulates apoptosis in prostate cancer cell lines. Biochim Biophys Acta 2013; 1832: 1613-1623
54 Romanuik TL, Wang G, Morozova O, Delaney A, Marra MA, Sadar MD. LNCaP Atlas: gene expression associated with in vivo progression to castration-recurrent prostate cancer. BMC Med Genomics 2010; 3: 43
55 Song J, Ahn C, Chun CH, Jin EJ. A long non-coding RNA, GAS5, plays a critical role in the regulation of miR-21 during osteoarthritis. J Orthop Res 2014; 32: 1628-1635
56 Nader N, Chrousos GP, Kino T. Interactions of the circadian CLOCK system and the HPA axis. Trends Endocrinol Metab 2010; 21: 277-286