Identification of an NF-κB p50/p65-responsive site in the human MIR155HG promoter

BMC Molecular Biology

Thomas D Gilmore¹  Iosif Vardinogiannis¹  Ryan C Thompson¹ 

[1] Department of Biology, Boston University, Boston, MA 02215, USA

关键词: Transcriptional activation;    Promoter;    NF-kappaB;    BIC;    MIR155HG;    miR-155;   

Others  :  1090627
DOI  :  10.1186/1471-2199-14-24

 received in 2013-05-13, accepted in 2013-09-16,  发布年份 2013

【 摘 要 】

Background

MicroRNA-155 (miR-155) is the diced product of the MIR155HG gene. miR-155 regulates the expression of many immune-specific transcripts, is overexpressed in many human lymphomas, and has oncogenic activity in mouse transgenic models. MIR155HG has been proposed to be a target gene for transcription factor NF-κB largely due to the positive correlation between high nuclear NF-κB activity and increased miR-155 expression following treatment with NF-κB inducers or in subsets of hematopoietic cancers. Nevertheless, direct regulation of the human MIR155HG promoter by NF-κB has not been convincingly demonstrated previously.

Results

This report shows that induction of NF-κB activity rapidly leads to increased levels of both primary MIR155HG mRNA and mature miR-155 transcripts. We have mapped an NF-κB-responsive element to a position approximately 178 nt upstream of the MIR155HG transcription start site. The -178 site is specifically bound by the NF-κB p50/p65 heterodimer and is required for p65-induced reporter gene activation. Moreover, the levels of miR-155 in nine human B-lymphoma cell lines generally correlate with increased nuclear NF-κB proteins.

Conclusion

Overall, the identification of an NF-κB-responsive site in the MIR155HG proximal promoter suggests that MIR155HG is a direct NF-κB target gene in vivo. Understanding NF-κB-mediated regulation of miR-155 could lead to improved immune cell-related diagnostic tools and targeted therapies.

【 授权许可】

   
2013 Thompson et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

【 参考文献 】

• [1]Faraoni I, Antonetti FR, Cardone J, Bonmassar E: miR-155 gene: a typical multifunctional microRNA. Biochim Biophys Acta 2009, 1792:497-505.
• [2]O’Connell RM, Rao DS, Chaudhuri AA, Baltimore D: Physiological and pathological roles for microRNAs in the immune system. Nat Rev Immunol 2010, 10:111-122.
• [3]Leng RX, Pan HF, Qin WZ, Chen GM, Ye DQ: Role of microRNA-155 in autoimmunity. Cytokine Growth Factor Rev 2011, 22:141-147.
• [4]Tili E, Michaille JJ, Croce CM: MicroRNAs play a central role in molecular dysfunctions linking inflammation with cancer. Immunol Rev 2013, 253:167-184.
• [5]Taganov KD, Boldin MP, Chang KJ, Baltimore D: NF-κB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses. Proc Natl Acad Sci USA 2006, 33:12481-12486.
• [6]O’Connell RM, Taganov KD, Boldin MP, Cheng G, Baltimore D: MicroRNA-155 is induced during the macrophage inflammatory response. Proc Natl Acad Sci USA 2007, 104:1604-1609.
• [7]Thompson RC, Herscovitch M, Zhao I, Ford TJ, Gilmore TD: NF-κB down-regulates expression of the B-lymphoma marker CD10 through a miR-155/PU.1 pathway. J Biol Chem 2011, 286:1675-1682.
• [8]Zhang J, Zhao H, Chen J, Xia B, Jin Y, Wei W, Shen J, Huang YL: Interferon-β-induced miR-155 inhibits osteoclast differentiation by targeting SOCS1 and MITF. FEBS Lett 2012, 586:3255-3262.
• [9]O’Connell RM, Rao DS, Baltimore D: microRNA regulation of inflammatory responses. Annu Rev Immunol 2012, 30:295-312.
• [10]Thai TH, Calado DP, Casola S, Ansel KM, Xiao C, Xue Y, Murphy A, Frendewey D, Valenzuela D, Kutok JL, Schmidt-Supprian M, Rajewsky N, Yancopoulos G, Rao A, Rajewsky K: Regulation of the germinal center response by microRNA-155. Science 2007, 316:604-608.
• [11]Rodriguez A, Vigorito E, Clare S, Warren MV, Couttet P, Soond DR, van Dongen S, Grocock RJ, Das PP, Miska EA, Vetrie D, Okkenhaug K, Enright AJ, Dougan G, Turner M, Bradley A: Requirement of bic/microRNA-155 for normal immune function. Science 2007, 316:608-611.
• [12]Eis PS, Tam W, Sun L, Chadburn A, Li Z, Gomez MF, Lund E, Dahlberg JE: Accumulation of miR-155 and BIC RNA in human B cell lymphomas. Proc Natl Acad Sci USA 2005, 102:3627-3632.
• [13]Kluiver J, Poppema S, de Jong D, Blokzijl T, Harms G, Jacobs S, Kroesen B-J, van den Berg A: BIC and miR-155 are highly expressed in Hodgkin, primary mediastinal and diffuse large B cell lymphomas. J Pathol 2005, 207:243-249.
• [14]Lawrie CH, Soneji S, Marafioti T, Cooper CDO, Palazzo S, Paterson JC, Cattan H, Enver T, Mager R, Boultwood J, Wainscoat JS, Hatton CSR: MicroRNA expression distinguishes between germinal center B cell-like and activated B cell-like subtypes of diffuse large B cell lymphoma. Int J Cancer 2007, 121:1156-1161.
• [15]Rai D, Karanti S, Jung I, Dahia PLM, Aguiar RCT: Coordinated expression of microRNA-155 and predicted target genes in diffuse large B-cell lymphoma. Cancer Genet Cytogenet 2008, 181:8-15.
• [16]Costinean S, Zanesi N, Pekarsky Y, Tili E, Volinia S, Heerema N, Croce CM: Pre-B cell proliferation and lymphoblastic leukemia/high-grade lymphoma in Eμ-miR155 transgenic mice. Proc Natl Acad Sci USA 2006, 103:7024-7029.
• [17]O’Connell RM, Rao DS, Chaudhuri AA, Boldin MP, Taganov KD, Nicoll J, Paquette RL, Baltimore D: Sustained expression of microRNA-155 in hematopoietic stem cells causes a myeloproliferative disorder. J Exp Med 2008, 205:585-594.
• [18]Tam W: Identification and characterization of human BIC, a gene on chromosome 21 that encodes a noncoding RNA. Gene 2001, 274:157-167.
• [19]Elton TS, Selemon H, Elton SM, Parinandi NL: Regulation of MIR155 host gene in physiological and pathological processes. Gene 2012. in press
• [20]Dorsett Y, McBride KM, Jankovic M, Gazumyan A, Thai T-H, Robbiani DF, Di Virgilio M, Reina San-Martin B, Heidkamp G, Schwickert TA, Eisenreich T, Rajewsky K, Nussenzweig MC: MicroRNA-155 suppresses activation-induced cytidine deaminase-mediated Myc-Igh translocation. Immunity 2008, 28:630-638.
• [21]Yin Q, McBride J, Fewell C, Lacey M, Wang X, Lin Z, Cameron J, Flemington EK: MicroRNA-155 is an Epstein-Barr virus-induced gene that modulates Epstein-Barr virus-regulated gene expression pathways. J Virol 2008, 82:5295-5306.
• [22]Gatto G, Rossi A, Rossi D, Kroening S, Bonatti S, Mallardo M: Epstein-Barr virus latent membrane protein 1 trans-activates miR-155 transcription through the NF-κB pathway. Nucleic Acids Res 2008, 36:6608-6619.
• [23]Cremer TJ, Fatehchand K, Shah P, Gillette D, Patel H, Marsh RL, Besecker BY, Rajaram MVS, Cormet-Boyaka E, Kanneganti T-D, Schlesinger LS, Butchar JP, Tridandapani S: MiR-155 induction by microbes/microbial ligands requires NF-κB-dependent de novo protein synthesis. Front Cell Infect Microbiol 2012, 2:73.
• [24]Leeman JR, Weniger MA, Barth TF, Gilmore TD: Deletion analysis and alternative splicing define a transactivation inhibitory domain in human oncoprotein REL. Oncogene 2008, 27:6770-6781.
• [25]Davis RE, Brown KD, Siebenlist U, Staudt LM: Constitutive nuclear factor kappaB activity is required for survival of activated B cell-like diffuse large B cell lymphoma cells. J Exp Med 2001, 194:1861-1874.
• [26]Ngo VN, Davis RE, Lamy L, Yu X, Zhao H, Lenz G, Lam LT, Dave S, Yang L, Powell J, Staudt LM: A loss-of-function RNA interference screen for molecular targets in cancer. Nature 2006, 441:106-110.
• [27]Singh RR, Kim JE, Davuluri Y, Drakos E, Cho-Vega JH, Amin HM, Vega F: Hedgehog signaling pathway is activated in diffuse large B-cell lymphoma and contributes to tumor cell survival and proliferation. Leukemia 2010, 24:1025-1036.
• [28]Carter KL, Cahir-McFarland E, Kieff E: Epstein-Barr virus-induced changes in B-lymphocyte gene expression. J Virol 2012, 76:10427-10436.
• [29]Contreras-Salazar B, Ehlin-Henriksson B, Klein G, Masucci MG: Up regulation of the Epstein-Barr virus (EBV)-encoded membrane protein LMP in the Burkitt’s lymphoma line Daudi after exposure to n-butyrate and after EBV superinfection. J Virol 1990, 64:5441-5447.
• [30]Zhang W, Bardwell PD, Woo CJ, Poltoratsky V, Scharff MD, Martin A: Clonal instability of V region hypermutation in the Ramos Burkitt’s lymphoma cell line. Int Immunol 2001, 13:1175-1184.
• [31]Emmerich F, Meiser M, Hummel M, Demel G, Foss H-D, Jundt F, Mathas S, Krappmann D, Scheidereit C, Stein H, Dörken B: Overexpression of I kappa B alpha without inhibition of NF-κB activity and mutations in the I kappa B alpha gene in Reed-Sternberg cells. Blood 1999, 94:3129-3134.
• [32]Chin M, Herscovitch M, Zhang N, Waxman DJ, Gilmore TD: Overexpression of an activated REL mutant enhances the transformed state of the human B-lymphoma BJAB cell line and alters its gene expression profile. Oncogene 2009, 28:2100-2111.
• [33]Kalaitzidis D, Davis RE, Rosenwald A, Staudt LM, Gilmore TD: The human B-cell lymphoma cell line RC-K8 has multiple genetic alterations that dysregulate the Rel/NF-κB signal transduction pathway. Oncogene 2002, 21:8759-8768.
• [34]Chang TK, Waxman DJ: Pregnane X receptor-mediated transcription. Methods Enzymol 2005, 400:588-598.
• [35]Chen C, Ridzon DA, Broomer AJ, Zhou Z, Lee DH, Nguyen JT, Barbisin M, Xu NL, Mahuvakar VR, Andersen MR, Lao KQ, Livak KJ, Guegler KJ: Real-time quantification of microRNAs by stem-loop RT-PCR. Nucleic Acids Res 2005, 33:e179.
• [36]PROMO Transcription Factor Binding Site Virtual Laboratoryhttp://alggen.lsi.upc.es/cgi-bin/promo_v3/promo/promoinit.cgi?dirDB=TF_8.3 webcite
• [37]Transcriptional Regulatory Element Database (TRED)http://rulai.cshl.edu/cgi-bin/TRED/tred.cgi?process=home webcite
• [38]Liang M-C, Bardhan S, Pace EA, Rosman D, Beutler JA, Porco JA Jr, Gilmore TD: Inhibition of transcription factor NF-κB signaling proteins IKKβ and p65 through specific cysteine residues by epoxyquinone A monomer: correlation with its anti-cancer cell growth activity. Biochem Pharmacol 2006, 71:634-645.
• [39]Yeo AT, Porco JA Jr, Gilmore TD: Bcl-XL, but not Bcl-2, can protect B-lymphoma cell lines from parthenolide-induced apoptosis. Cancer Lett 2012, 318:53-60.
• [40]Bustin SA, Benes V, Garson JA, Hellemans J, Huggett J, Kubista M, Mueller R, Nolan T, Pfaffl MW, Shipley GL, Vandesompele J, Wittwer CT: The MIQE guidelines: Minimum information for publication of quantitative real-time PCR experiments. Clin Chem 2009, 55:611-622.
• [41]Bren GD, Solan NJ, Miyoshi H, Pennington KN, Pobst LJ, Paya CV: Transcription of the RelB gene is regulated by NF-κB. Oncogene 2001, 53:7722-7733.
• [42]Eliopoulos AG, Young LS: LMP1 structure and signal transduction. Sem Cancer Biol 2001, 11:435-444.
• [43]Thorley-Lawson DA: Epstein-Barr virus: exploiting the immune system. Nat Rev Immunol 2001, 1:75-82.
• [44]Siggers T, Chang AB, Teixira A, Wong D, Williams KJ, Ahmed B, Ragoussis J, Udalova IA, Smale ST, Bulyk ML: Principles of dimer-specific gene regulation revealed by a comprehensive characterization of NF-κB family DNA binding. Nat Immunol 2011, 13:95-102.
• [45]Paxton LLL, Li L-J, Secor V, Duff JL, Naik SM, Shibagaki N, Caughman SW: Flanking sequences for the human intercellular adhesion molecule-1 NF-κB response element are necessary for tumor necrosis factor α-induced gene expression. J Biol Chem 1997, 272:15928-15935.
• [46]Goto M, Katayama KI, Shirakawa F, Tanaka I: Involvement of NF-κB p50/p65 heterodimer in activation of the human pro-interleukin-1β gene at two subregions of the upstream enhancer element. Cytokine 1999, 11:16-28.
• [47]Wang J, Gu Z, Ni P, Qiao Y, Chen C, Liu X, Lin J, Chen N, Fan Q: NF-kappaB P50/P65 hetero-dimer mediates differential regulation of CD166/ALCAM expression via interaction with micoRNA-9 after serum deprivation, providing evidence for a novel negative auto-regulatory loop. Nucleic Acids Res 2011, 39:6440-6455.
• [48]Kluiver J, van den Berg A, de Jong D, Blokzijl T, Harms G, Bouwman E, Jacobs S, Poppema S, Kroesen B-J: Regulation of pri-microRNA BIC transcription and processing in Burkitt lymphoma. Oncogene 2007, 26:3769-3776.
• [49]Rahadiani N, Takakuwa T, Tresnasari K, MOrii E, Aozaisa K: Latent membrane protein-1 of Epstein-Barr virus induces the expression of B-cell integration cluster, a precurson of microRNA-155 of B lymphoma cell lines. Biochem Biophys Res Commun 2008, 377:579-583.
• [50]Liang M-C, Bardhan S, Porco JA Jr, Gilmore TD: The synthetic epoxyquinoids jesterone dimer and epoxyquinone A monomer induce apoptosis and inhibit REL (human c-Rel) DNA binding in an IκBα-deficient diffuse large B-cell lymphoma cell line. Cancer Lett 2005, 241:69-78.
• [51]Martone R, Euskirchen G, Bertone P, Hartman S, Royce TE, Luscombe NM, Rinn JL, Nelson K, Miller P, Gerstein M, Weissman S, Snyder M: Distribution of NF-κB-binding sites across the human chromosome 22. Proc Natl Acad Sci USA 2003, 21:12247-12252.
• [52]Lim C-A, Yao F, Wong JJ-Y, George J, Xu H, Chiu KP, Sung W-K, Lipovich L, Vega VB, Chen J, Shahab A, Zhao XD, Hibberd M, Wei C-L, Lim B, Ng H-H, Ruan Y, Chin K-C: Genome-wide mapping of RELA(p65) binding identifies E2F1 as a transcriptional activator recruited by NF-κB upon TLR4 activation. Mol Cell 2007, 27:622-635.
• [53]Wang Z, Zang C, Cui K, Schones DE, Barski A, Peng W, Zhao K: Genome-wide mapping of HATs and HDACs reveals distinct functions in active and inactive genes. Cell 2009, 138:1019-1031.
• [54]Ramos YFM, Hestand MS, Verlaan M, Krabbendam E, Ariyurek Y, van Galen M, van Dam H, van Ommen G-JB, den Dunnen JT, Zantema A, ‘t Hoen PAC: Genome-wide assessment of differential roles for p300 and CBP in transcription regulation. Nucleic Acids Res 2010, 38:5396-5408.