Interplay between NRF1, E2F4 and MYC transcription factors regulating common target genes contributes to cancer development and progression

Abstract

Background

Nuclear respiratory factor 1 (NRF1), historically perceived as a protein regulating genes controlling mitochondrial biogenesis, is now widely recognized as a multifunctional protein and as a key player in the transcriptional modulation of genes implicated in various cellular functions. Here, we present emerging data supporting novel roles of NRF1 in cancer development and progression through its interplay with the transcription factors E2F4 and MYC. To identify common human NRF1, E2F4 and MYC target genes, we analyzed the Encyclopedia of DNA Elements (ENCODE) NRF1 ChIP-Seq data. By doing so, we identified 9253 common target genes with NRF1, E2F4 and MYC binding motifs. NRF1 binding motifs were found to be present in genes operating in signaling pathways governing all hallmarks of malignant transformation and progression, including proliferation, invasion, self-renewal and apoptosis.

Conclusions

In addition to controlling mitochondrial biogenesis NRF1, in conjunction with E2F4 and MYC, may play a critical role in the acquisition of human cancer characteristics. Additionally, NRF1 may orchestrate both MYC and E2F4 to regulate common target genes linked to multiple networks in the development and progression of cancer. A comprehensive understanding of this dynamic interplay will set the stage, not only for the design of novel treatment strategies, but also for the discovery of pan-cellular transcription factor regulatory strategies to predict cancer risk, therapy response and patient prognosis.

This is a preview of subscription content, log in to check access.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

References

  1. 1.

    J. Wang, Q. Liu, J. Sun, Y. Shyr, Disrupted cooperation between transcription factors across diverse cancer types. BMC Genomics 17, 560 (2016)

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  2. 2.

    S.A. Lambert, A. Jolma, L. Campitelli, P. Das, T. Yin, M. Albu, X. Chen, J. Taipale, T. Hughes, M. Weirauch, The human transcription factors. Cell 172, 650–665 (2018)

    PubMed  CAS  Article  Google Scholar 

  3. 3.

    M.M. Falco, M. Bleda, J. Carbonell-Caballero, J. Dopazo, The pan-cancer pathological regulatory landscape. Nature Sci Rep 6 (2016)

  4. 4.

    C.V. Dang, MYC on the path to cancer. Cell 149, 22–35 (2012)

    PubMed  PubMed Central  CAS  Article  Google Scholar 

  5. 5.

    V.O. Okoh, Q. Felty, J. Parkash, R. Poppiti, D. Roy, Reactive oxygen species via redox signaling to PI3K/AKT pathway contribute to the malignant growth of 4-hydroxy estradiol-transformed mammary epithelial cells. PLoS One 8, e54206 (2011)

    Article  CAS  Google Scholar 

  6. 6.

    V.O. Okoh, N.A. Garba, R.B. Penney, J. Das, A. Deoraj, K. Singh, S. Sarkar, Q. Felty, C. Yoo, R. Jackson, D. Roy, Redox signaling to nuclear regulatory proteins by reactive oxygen species contributes to estrogen-induced growth of breast cancer cells. British J Cancer 112, 1687–1702 (2015)

    CAS  Article  Google Scholar 

  7. 7.

    D. Roy, R. Tamuli, NRF1 (nuclear respiratory factor 1). Atlas of Genetics and Cytogenetics in Oncology and Haematology 13, 4 (2008)

    Google Scholar 

  8. 8.

    L. Gopalakrishnan, R.C. Scarpulla, Structure, expression, and chromosomal assignment of the human gene encoding nuclear respiratory factor 1. J Biol Chem 270, 18019–18025 (1995)

    PubMed  CAS  Article  Google Scholar 

  9. 9.

    R.C. Scarpulla, Transcriptional paradigms in mammalian mitochondrial biogenesis and function. Physiol Rev 88, 611–638 (2008)

    PubMed  CAS  Article  Google Scholar 

  10. 10.

    J.Y. Chan, X.L. Han, Y.W. Kan, Cloning of Nrf1, an NF-E2-related transcription factor, by genetic selection in yeast. Proc Natl Acad Sci U S A 90, 11371–11375 (1993)

    PubMed  PubMed Central  CAS  Article  Google Scholar 

  11. 11.

    V. Tiranti, E. Rossi, M. Rocchi, S. DiDonato, O. Zuffardi, M. Zeviani, The gene (NFE2L1) for human NRF-1, an activator involved in nuclear-mitochondrial interactions, maps to 7q32. Genomics 27, 555–557 (1995)

    PubMed  CAS  Article  Google Scholar 

  12. 12.

    R.C. Scarpulla, Nuclear control of respiratory chain expression by nuclear respiratory factors and PGC-1-related coactivator. Ann N Y Acad Sci 1147, 321–334 (2008)

    PubMed  PubMed Central  CAS  Article  Google Scholar 

  13. 13.

    J.S. Bassey, J.A.C. Efiok, B. Safer, A key transcription factor for eukaryotic initiation factor-2a is strongly homologous to developmental transcription factors and may link metabolic genes to cellular growth and development. J Biol Chem 269, 18921–18930 (1994)

    Google Scholar 

  14. 14.

    H. Cam, E. Balciunaite, A. Blais, A. Spektor, R.C. Scarpulla, R. Young, Y. Kluger, B.D. Dynlacht, A common set of gene regulatory networks links metabolism and growth inhibition. Mol Cell 16, 399–411 (2004)

    PubMed  CAS  Article  Google Scholar 

  15. 15.

    J. Satoh, N. Kawana, Y. Yamamoto, Pathway analysis of ChIP-Seq-based NRF1 target genes suggests a logical hypothesis of their involvement in the pathogenesis of neurodegenerative diseases. Gene Reg Syst Biol 7, 139–152 (2013)

    Google Scholar 

  16. 16.

    C. Amin, A.J. Wagner, N. Hay, Sequence-specific transcriptional activation by Myc and repression by max. Mol Cell Biol 13, 383–390 (1993)

    PubMed  PubMed Central  CAS  Article  Google Scholar 

  17. 17.

    A.L. Gartel, K. Shchors, Mechanisms of c-myc-mediated transcriptional repression of growth arrest genes. Exp Cell Res 283, 17–21 (2003)

    PubMed  CAS  Article  Google Scholar 

  18. 18.

    B. Lüscher, Function and regulation of the transcription factors of the Myc/max/mad network. Gene 277, 1–14 (2001)

    PubMed  Article  Google Scholar 

  19. 19.

    C.V. Dang, S.B. McMahon, Emerging concepts in the analysis of transcriptional targets of the MYC oncoprotein: Are the targets targetable? Genes & Cancer 1, 560–567 (2010)

    Article  CAS  Google Scholar 

  20. 20.

    W. Tansey, P. Mammalian, MYC proteins and cancer. New Journal of Science, Hindawi 757534, 1–27 (2014)

    Google Scholar 

  21. 21.

    H.Z. Chen, S.Y. Tsai, G. Leone, Emerging roles of E2Fs in cancer: An exit from cell cycle control. Nature Rev Cancer 9, 785–797 (2009)

    CAS  Article  Google Scholar 

  22. 22.

    S. Schwemmle, P. Pfeifer, Genomic structure and mutation screening of the E2F4 gene in human tumors. Int J Cancer 86, 672–677 (2000)

    PubMed  CAS  Article  Google Scholar 

  23. 23.

    P.J. Iaquinta, J.A. Lees, Life and death decisions by the E2F transcription factors. Curr Opin Cell Biol 19, 649–657 (2007)

    PubMed  PubMed Central  CAS  Article  Google Scholar 

  24. 24.

    S. Skirnisdottir, G. Eiriksdottir, T. Baldursson, R.B. Barkardottir, V. Egilsson, S. Ingvarrson, High frequency of allelic imbalance at chromosome region 16q22-23 in human breast cancer: Correlation with high PgR and low S phase. Int J Cancer 64, 112–116 (1995)

    PubMed  CAS  Article  Google Scholar 

  25. 25.

    X. Zhong, H. Hemmi, J. Koike, K. Tsujita, H. Shimatake, Various AGC repeat numbers in the coding region of the human transcription factor gene E2F-4. Hum Mut 15, 296–297 (1999)

    Article  Google Scholar 

  26. 26.

    N. Palmer, P. Kaldis, Regulation of the embryonic cell cycle during mammalian preimplantation development. Curr Top Dev Biol 120, 1–53 (2016)

    PubMed  CAS  Article  Google Scholar 

  27. 27.

    Z. Kherrouche, D.Y. Launoit, D. Monte, The NRF-1/α-PAL transcription factor regulates human E2F6 promoter activity. Biochem J 383, 529–536 (2004)

    PubMed  PubMed Central  CAS  Article  Google Scholar 

  28. 28.

    S.T. Shors, B.J.S. Effiok, S.J. Harkin, B. Safer, Formation of pal/max heterodimers synergistically activates the eif2 promoter. J Biol Chem 273, 529–536 (1998)

    Article  Google Scholar 

  29. 29.

    A.B. West, G. Kapatos, C. O’Farrell, F. Gonzalez-de-Chavez, K. Chiu, M.J. Farrer, N.T. Maidment, N-myc regulates parkin expression. J Biol Chem 279, 28896–28902 (2004)

    PubMed  CAS  Article  Google Scholar 

  30. 30.

    J.K. Das, D. Roy, Transcriptional regulation of chemokine receptor 4 (CXCR4) by nuclear respiratory factor 1 (NRF1) controls estrogen-induced malignant transformation of breast epithelial cells to breast cancer stem cells. Cancer Res 76, 3312 (2016)

    Article  Google Scholar 

  31. 31.

    J.M. Lin, P.J. Collins, N.D. Trinklein, Y. Fu, H. Xi, R.M. Myers, Z. Weng, Transcription factor binding and modified histones in human bidirectional promoters. Genome Res 17, 818–827 (2007)

    PubMed  PubMed Central  CAS  Article  Google Scholar 

  32. 32.

    Y.M. Oh, J.K. Kim, S. Choi, J.Y. Yoo, Identification of co-occurring transcription factor binding sites from DNA sequence using clustered position weight matrices. Nucl Acids Res 40, e38–e38 (2012)

    PubMed  CAS  Article  Google Scholar 

  33. 33.

    R. Elkon, C. Linhart, R. Sharan, R. Shamir, Y. Shiloh, Genome-wide in silico identification of transcriptional regulators controlling the cell cycle in human cells. Genome Res 13, 773–780 (2003)

    PubMed  PubMed Central  CAS  Article  Google Scholar 

  34. 34.

    C. Benner, S. Konovalov, C. Mackintosh, K.R. Hutt, R. Stunnenberg, I. Garcia-Bassets, Decoding a signature-based model of transcription cofactor recruitment dictated by cardinal cis-regulatory elements in proximal promoter regions. PLoS Genet 9, e1003906 (2013)

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  35. 35.

    R.I. Sherwood, T. Hashimoto, C.W. O'Donnell, S. Lewis, A.A. Barkal, J.P. van Hoff, V. Karun, T. Jaakkola, D.K. Gifford, Discovery of directional and nondirectional pioneer transcription factors by modeling DNase profile magnitude and shape. Nature Biotech 32, 171–178 (2014)

    CAS  Article  Google Scholar 

  36. 36.

    M.D. Lavigne, G. Vatsellas, A. Polyzos, E. Mantouvalou, G. Sianidis, I. Maraziotis, M. Agelopoulos, D. Thanos, Composite macroH2A/NRF-1 nucleosomes suppress noise and generate robustness in gene expression. Cell Rep 11, 1090–1101 (2015)

    PubMed  CAS  Article  Google Scholar 

  37. 37.

    A. Ferraro, Altered primary chromatin structures and their implications in cancer development. Cell Oncol 39, 195–210 (2016)

    Article  Google Scholar 

  38. 38.

    F. Morrish, C. Giedt, & Hockenbery D. C-MYC apoptotic function is mediated by NRF-1 target genes. Genes Dev 17, 240–255 (2003)

    PubMed  PubMed Central  CAS  Article  Google Scholar 

  39. 39.

    H.B. Suliman, J.E. Keenan, C.A. Piantadosi, Mitochondrial quality-control dysregulation in conditional HO-1−/− mice. JCI Insight 2, e89676 (2017)

    PubMed  PubMed Central  Article  Google Scholar 

  40. 40.

    C. Zhang, M. Lin, R. Wu, X. Wang, B. Yang, A.J. Levine, W. Hu, Z. Feng, Parkin, a p53 target gene, mediates the role of p53 in glucose metabolism and the Warburg effect. Proc Natl Acad Sci U S A 108, 16259–16264 (2011)

    PubMed  PubMed Central  CAS  Article  Google Scholar 

  41. 41.

    A. Soufi, G. Donahue, K.S. Zaret, Facilitators and impediments of the pluripotency reprogramming factors' initial engagement with the genome. Cell 151, 994–1004 (2012)

    PubMed  PubMed Central  CAS  Article  Google Scholar 

  42. 42.

    J.D. Lin, Minireview: The PGC-1 coactivator networks: Chromatin-remodeling and mitochondrial energy metabolism. Mol Endocrin 23, 2–10 (2009)

    CAS  Article  Google Scholar 

  43. 43.

    W.-S. Tzou, Identification of potential E2F target genes through cis-regulatory modules derived from chromatin immunoprecipitation microarray data. Fooyin J Health Sci 2, 66–70 (2010)

    CAS  Article  Google Scholar 

  44. 44.

    H. Liu, X. Tang, A. Srivastava, T. Pecot, P. Daniel, B. Hemmelgarn, S. Reyes, N. Fackler, A. Bajwa, R. Kladney, C. Koivisto, Z. Chen, Q. Wang, K. Huang, R. Machiraju, M.T. Saenz-Robles, P. Cantalupo, J.M. Pipas, G. Leone, Redeployment of Myc and E2f1-3 drives Rb-deficient cell cycles. Nature Cell Biol 17, 1036–1048 (2015)

    PubMed  Article  CAS  Google Scholar 

  45. 45.

    C.R. Chen, Y. Kang, P.M. Siegel, J. Massagué, E2F4/5 and p107 as Smad cofactors linking the TGFβ receptor to c-myc repression. Cell 110, 19–32 (2002)

    PubMed  CAS  Article  Google Scholar 

  46. 46.

    H. Ogawa, K.I. Ishiguro, S. Gaubatz, D.M. Livingston, Y. Nakatani, A complex with chromatin modifiers that occupies E2F and Myc responsive genes in G0 cells. Science 296, 1132–1136 (2002)

    PubMed  CAS  Article  Google Scholar 

  47. 47.

    R.E. Rempel, S. Mori, M. Gasparetto, M.A. Glozak, E.R. Andrechek, S.B. Adler, N.M. Laakso, A.S. Lagoo, R. Storms, C. Smith, J.R. Nevins, A role for E2F activities in determining the fate of Myc-induced lymphomagenesis. PLoS Genet 5, e1000640 (2009)

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  48. 48.

    A. Fortunato, The role of hERG1 ion channels in epithelial-mesenchymal transition and the capacity of riluzole to reduce cisplatin resistance in colorectal cancer cells. Cell Oncol 40, 367–378 (2017)

    CAS  Article  Google Scholar 

  49. 49.

    A. Sathyanarayanan, K.S. Chandrasekaran, D. Karunagaran, microRNA-145 modulates epithelial-mesenchymal transition and suppresses proliferation, migration and invasion by targeting SIP1 in human cervical cancer cells. Cell Oncol 40, 119–131 (2017)

    CAS  Article  Google Scholar 

  50. 50.

    S. Bugide, V.K. Gonugunta, V. Penugurti, V.L. Malisetty, R.K. Vadlamudi, B. Manavathi, HPIP promotes epithelial-mesenchymal transition and cisplatin resistance in ovarian cancer cells through PI3K/AKT pathway activation. Cell Oncol 40, 133–144 (2017)

    CAS  Article  Google Scholar 

  51. 51.

    M. Mohrin, J. Shin, Y. Liu, K. Brown, H. Luo, Y. Xi, C.M. Haynes, D. Chen, Stem cell aging. A mitochondrial UPR-mediated metabolic checkpoint regulates hematopoietic stem cell aging. Science 347, 1374–1377 (2015)

    PubMed  PubMed Central  CAS  Article  Google Scholar 

  52. 52.

    J. Vazquez, J. Das, D. Roy, Estrogen and nuclear respiratory factor 1 act as joint mediators of redox modulation and stem cell aging that contribute in the pathogenesis of breast cancer. Cancer Res 76, 3322 (2016)

    Article  Google Scholar 

  53. 53.

    K. Bhawe, J. Das, C. Yoo, and D. Roy, NRF1 regulated gene-network characterizing chemical toxicity through TF effects in brain cancer. In: The Toxicologist: Supplement to Toxicological Sciences, 150, Abstract No. 1961, Pp 234, (2018)

  54. 54.

    M. Preciados, C. Yoo, D. Roy, Estrogenic endocrine disrupting chemicals influencing NRF1 regulated gene networks in the development of complex human brain diseases. Int J Mol Sci 17, E2086 (2016)

    PubMed  Article  CAS  Google Scholar 

  55. 55.

    J. Wang, H. Wang, Z. Li, Q. Wu, J.D. Lathia, R.E. McLendon, A.B. Hjelmeland, J.N. Rich, C-Myc is required for maintenance of glioma cancer stem cells. PLoS One 3, e3769 (2008)

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  56. 56.

    P. Sancho, D. Barneda, C. Heeschen, Hallmarks of cancer stem cell metabolism. Br J Cancer 114, 1305–1312 (2016)

    PubMed  PubMed Central  CAS  Article  Google Scholar 

  57. 57.

    S. Galardi, M. Savino, F. Scagnoli, S. Pellegatta, F. Pisati, F. Zambelli, B. Illi, D. Annibali, S. Beji, E. Orecchini, M.A. Alberelli, C. Apicella, R.A. Fontanella, A. Michienzi, G. Finocchiaro, M.G. Farace, G. Pavesi, S.A. Ciafrè, S. Nasi, Resetting cancer stem cell regulatory nodes upon MYC inhibition. EMBO Rep 17, 1872–1889 (2016)

    PubMed  PubMed Central  CAS  Article  Google Scholar 

  58. 58.

    R. Scognamiglio, N. Cabezas-Wallscheid, M.C. Thier, S. Altamura, A. Reyes, A.M. Prendergast, D. Baumgartner, L.S. Carnevalli, A. Atzberger, S. Haas, L. von Paleske, T. Boroviak, P. Worsdorfer, M.A. Essers, U. Kloz, R.N. Eisenman, F. Edenhofer, P. Bertone, W. Huber, F. van der Hoeven, A. Smith, A. Trumpp, Myc depletion induces a pluripotent dormant state mimicking diapause. Cell 164, 668–680 (2016)

    PubMed  PubMed Central  CAS  Article  Google Scholar 

  59. 59.

    H.C. Yeo, T.T. Beh, J.J. Quek, G. Koh, K.K. Chan, D.Y. Lee, Integrated transcriptome and binding sites analysis implicates E2F in the regulation of self-renewal in human pluripotent stem cells. PLoS One 6, e27231 (2011)

    PubMed  PubMed Central  CAS  Article  Google Scholar 

  60. 60.

    L.M. Julian, A. Blais, Transcriptional control of stem cell fate by E2Fs and pocket proteins. Front Genet 6, 161 (2015)

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  61. 61.

    S. Pauklin, P. Madrigal, A. Bertero, L. Vallier, Initiation of stem cell differentiation involves cell cycle-dependent regulation of developmental genes by cyclin D. Genes Dev 30, 421–433 (2016)

    PubMed  PubMed Central  CAS  Article  Google Scholar 

  62. 62.

    A. Diman, F. Poulain, J. Rodriguez, M. Purnelle, H. Episkopou, L. Bertrand, M. Francaux, L. Deldicque, A. Decottignies, Nuclear respiratory factor 1 and endurance exercise promote human telomere transcription. Science Adv 2, e1600031 (2016)

    Article  CAS  Google Scholar 

  63. 63.

    A. Ocampo, J.C.I. Belmonte, Holding your breath for longevity. Science 347, 1319–1320 (2015)

    PubMed  PubMed Central  CAS  Article  Google Scholar 

  64. 64.

    J.W. Hofmann, X. Zhao, M. De Cecco, A.L. Peterson, L. Pagliaroli, J. Manivannan, G.B. Hubbard, Y. Ikeno, Y. Zhang, B. Feng, X. Li, T. Serre, W. Qi, H. Van Remmen, R.A. Miller, K.G. Bath, R. de Cabo, H. Xu, N. Neretti, J.M. Sedivy, Reduced expression of MYC increases longevity and enhances healthspan. Cell 160, 477–488 (2015)

    PubMed  PubMed Central  CAS  Article  Google Scholar 

  65. 65.

    P. Hydbring, L.G. Larsson, Cdk2: A key regulator of the senescence control function of Myc. Aging 2, 244–250 (2010)

    PubMed  PubMed Central  CAS  Article  Google Scholar 

  66. 66.

    C. Park, I. Lee, W.K. Kang, E2F-1 is a critical modulator of cellular senescence in human cancer. Int J Mol Med 17, 715–720 (2006)

    PubMed  CAS  Google Scholar 

  67. 67.

    P. Iakova, S.S. Awad, N.A. Timchenko, Aging reduces proliferative capacities of liver by switching pathways of C/EBP growth arrest. Cell 113, 495–506 (2003)

    PubMed  CAS  Article  Google Scholar 

  68. 68.

    M. Vernier, V. Bourdeau, M.F. Gaumont-Leclerc, O. Moiseeva, V. Begin, F. Saad, A.M. Mes-Masson, G. Ferbeyre, Regulation of E2Fs and senescence by PML nuclear bodies. Genes Dev 25, 41–50 (2011)

    PubMed  PubMed Central  CAS  Article  Google Scholar 

  69. 69.

    J. Permuth-Wey, Y.A. Chen, Y.Y. Tsai, Z. Chen, X. Qu, J.M. Lancaster, H. Stockwell, G. Dagne, E. Iversen, H. Risch, J. Barnholtz-Sloan, J.M. Cunningham, R.A. Vierkant, B.L. Fridley, R. Sutphen, J. McLaughlin, S.A. Narod, E.L. Goode, J.M. Schildkraut, D. Fenstermacher, C.M. Phelan, T.A. Sellers, Inherited variants in mitochondrial biogenesis genes may influence epithelial ovarian cancer risk. Cancer Epidemiol Biomark Prev 20, 1131–114567 (2011)

    CAS  Article  Google Scholar 

  70. 70.

    W. Liu, B.H. Beck, K.S. Vaidya, K.T. Nash, K.P. Feeley, S.W. Ballinger, K.M. Pounds, W.L. Denning, A.R. Diers, A. Landar, A. Dhar, T. Iwakuma, D.R. Welch, Metastasis suppressor KISS1 seems to reverse the Warburg effect by enhancing mitochondrial biogenesis. Cancer Res 74, 954–963 (2014)

    PubMed  CAS  Article  Google Scholar 

  71. 71.

    M.M. Ivanova, K.H. Luken, A.S. Zimmer, F.L. Lenzo, R.J. Smith, M.W. Arteel, T.J. Kollenberg, K.A. Mattingly, C.M. Klinge, Tamoxifen increases nuclear respiratory factor 1 transcription by activating estrogen receptor β and AP-1 recruitment to adjacent promoter binding sites. FASEB J 25, 1402–1416 (2011)

    PubMed  PubMed Central  CAS  Article  Google Scholar 

  72. 72.

    D. Wang, J. Zhang, Y. Lu, Q. Luo, L. Zhu, Nuclear respiratory factor (NRF1) regulated hypoxia inducible factor 1alpha (HIF1a) under hypoxia in HEK293T. IUBMB Life 68, 748–755 (2016)

    PubMed  CAS  Article  Google Scholar 

  73. 73.

    L. Zhang, Q. Ding, Z. Wang, Nuclear respiratory factor 1 mediates the transcription initiation of insulin-degrading enzyme in a TATA box-binding protein-independent manner. PLoS One 7, e42035 (2012)

    PubMed  PubMed Central  CAS  Article  Google Scholar 

  74. 74.

    A.G. Vaiopoulos, K. Athanasoula, A.G. Papavassiliou, Epigenetic modifications in colorectal cancer: Molecular insights and therapeutic challenges. Biochim Biophys Acta 1842, 971–980 (2014)

    PubMed  CAS  Article  Google Scholar 

  75. 75.

    S. Sharma Saha, R. Roy Chowdhury, N.R. Mondal, B. Chakravarty, T. Chatterjee, S. Roy, S. Sengupta, Identification of genetic variation in the lncRNA HOTAIR associated with HPV16-related cervical cancer pathogenesis. Cell Oncol 39, 583–589 (2016)

    Article  CAS  Google Scholar 

  76. 76.

    M. Xu, C.E. Cross, J.T. Speidel, S.Z. Abdel-Rahman, MGMT DNA repair gene promoter/enhancer haplotypes alter transcription factor binding and gene expression. Cell Oncol 39, 435–447 (2016)

    CAS  Article  Google Scholar 

  77. 77.

    C. Gebhard, C. Benner, M. Ehrich, L. Schwarzfischer, E. Schilling, M. Klug, W. Dietmaier, C. Thiede, E. Holler, R. Andreesen, M. Rehli, General transcription factor binding at CpG islands in normal cells correlates with resistance to de novo DNA methylation in cancer cells. Cancer Res 70, 1398–1407 (2010)

    PubMed  CAS  Article  Google Scholar 

  78. 78.

    S.S. Hammoud, B.R. Cairns, D.A. Jones, Epigenetic regulation of colon cancer and intestinal stem cells. Curr Opin Cell Biol 25, 177–183 (2013)

    PubMed  PubMed Central  CAS  Article  Google Scholar 

  79. 79.

    A. Wolfer, S. Ramaswamy, MYC and metastasis. Cancer Res 71, 2034–2037 (2011)

    PubMed  PubMed Central  CAS  Article  Google Scholar 

  80. 80.

    H. Liu, D.C. Radisky, D. Yang, R. Xu, E.S. Radisky, M.J. Bissell, J.M. Bishop, MYC suppresses cancer metastasis by direct transcriptional silencing of [alpha]v and [beta]3 integrin subunits. Nature Cell Biol 14, 567–574 (2012)

    PubMed  CAS  Article  Google Scholar 

  81. 81.

    M. Jung, A.J. Russell, B. Liu, J. George, P.Y. Liu, T. Liu, A. DeFazio, D.D. Bowtell, A. Oberthuer, W.B. London, J.I. Fletcher, M. Haber, M.D. Norris, M.J. Henderson, A Myc activity signature predicts poor clinical outcomes in Myc-associated cancers. Cancer Res 15, 971–981 (2017)

    Article  CAS  Google Scholar 

  82. 82.

    U.R. Rapp, C. Korn, F. Ceteci, C. Karreman, K. Luetkenhaus, V. Serafin, E. Zanucco, I. Castro, T. Potapenko, MYC is a metastasis gene for non-small-cell lung cancer. PLoS One 4, e6029 (2009)

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  83. 83.

    L. Fagnocchi, A. Cherubini, H. Hatsuda, A. Fasciani, S. Mazzoleni, V. Poli, V. Berno, R. Rossi, R. Reinbold, M. Endele, T. Schroeder, M. Rocchigiani, Z. Szkarlat, S. Oliviero, S. Dalton, A. Zippo, A Myc-driven self-reinforcing regulatory network maintains mouse embryonic stem cell identity. Nat Commun 7, 11903 (2016)

    PubMed  PubMed Central  CAS  Article  Google Scholar 

  84. 84.

    H.B. Suliman, T.E. Sweeney, C.M. Withers, C.A. Piantadosi, Co-regulation of nuclear respiratory factor-1 by NFkappaB and CREB links LPS-induced inflammation to mitochondrial biogenesis. J Cell Science 123, 2565–2575 (2010)

    PubMed  CAS  Article  Google Scholar 

  85. 85.

    M.L. Boland, A.H. Chourasia, K.F. Macleod, Mitochondrial dysfunction in cancer. Front Oncol 3, 292 (2013)

    PubMed  PubMed Central  Article  Google Scholar 

  86. 86.

    K.E. Wiese, S. Walz, B. von Eyss, E. Wolf, D. Athineos, O. Sansom, M. Eilers, Cold Spring Harbor Perspectives in Medicine 3, a014290 (2013)

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  87. 87.

    T.C. Chang, D. Yu, Y.S. Lee, E.A. Wentzel, D.E. Arking, K.M. West, C.V. Dang, A. Thomas-Tikhonenko, J.T. Mendell, Widespread microRNA repression by Myc contributes to tumorigenesis. Nature Genet 40, 43–50 (2008)

    PubMed  CAS  Article  Google Scholar 

  88. 88.

    C. Bertoli, J.M. Skotheim, R.A. de Bruin, Control of cell cycle transcription during G1 and S phases. Nature Rev Mol Cell Biol 14, 518–528 (2013)

    CAS  Article  Google Scholar 

  89. 89.

    G. Yao, Modelling mammalian cellular quiescence. Interface Focus 4, 3 (2014)

    Article  Google Scholar 

  90. 90.

    S. Zheng, J. Moehlenbrink, Y.C. Lu, L.P. Zalmas, C.A. Sagum, S. Carr, J.F. McGouran, L. Alexander, O. Fedorov, S. Munro, B. Kessler, M.T. Bedford, Q. Yu, N.B.L. Thangue, Arginine methylation-dependent reader-writer interplay governs growth control by E2F-1. Mol Cell 52, 37–51 (2013)

    PubMed  PubMed Central  CAS  Article  Google Scholar 

  91. 91.

    B.P. Coe, K.L. Thu, S.A. Ronen, E.A. Vucic, A.F. Gazdar, S. Lam, M.S. Tsao, W.L. Lam, Genomic deregulation of the E2F/Rb pathway leads to activation of the oncogene EZH2 in small cell lung cancer. PLoS One 8, e71670 (2013)

    PubMed  PubMed Central  CAS  Article  Google Scholar 

  92. 92.

    H.Z. Chen, M.M. Ouseph, J. Li, T. Pécot, V. Chokshi, L. Kent, S. Bae, M. Byrne, C. Duran, G. Comstock, P. Trikha, M. Mair, S. Senapati, C.K. Martin, S. Gandhi, N. Wilson, B. Liu, Y.W. Huang, J.C. Thompson, S. Raman, S. Singh, M. Leone, R. Machiraju, K. Huang, X. Mo, S. Fernandez, I. Kalaszczynska, D.J. Wolgemuth, P. Sicinski, T. Huang, V. Jin, G. Leone, Canonical and atypical E2Fs regulate the mammalian endocycle. Nature Cell Biol 14, 1192–1202 (2012)

    PubMed  CAS  Article  Google Scholar 

  93. 93.

    J. Johnson, B. Thijssen, U. McDermott, M. Garnett, L.F.A. Wessels, R. Bernards, Targeting the RB-E2F pathway in breast cancer. Oncogene 35, 4829–4835 (2016)

    PubMed  PubMed Central  CAS  Article  Google Scholar 

  94. 94.

    D.P. Hollern, J. Honeysett, R.D. Cardiff, E.R. Andrechek, The E2F transcription factors regulate tumor development and metastasis in a mouse model of metastatic breast cancer. Mol Cell Biol 34, 3229–3240 (2014)

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  95. 95.

    E.R. Andrechek, HER2/Neu tumorigenesis and metastasis is regulated by E2F activator trancription factors. Oncogene 34, 217–225 (2015)

    PubMed  CAS  Article  Google Scholar 

  96. 96.

    A. Mathe, M.W. Brown, B. Morten, J.F. Forbes, S.G. Braye, K.A. Avery-Kiejda, R.J. Scott, Novel genes associated with lymph node metastasis in triple negative breast cancer. Nature Sci Rep 5, 15832 (2015)

  97. 97.

    H. Garneau, L. Alvarez, M.C. Paquin, C. Lussier, C. Rancourt, E. Tremblay, J.F. Beaulieu, N. Rivard, Nuclear expression of E2F4 induces cell death via multiple pathways in normal human intestinal epithelial crypt cells but not in colon cancer cells. Am J Physiol Gastrointest Liver Physiol 293, G758–G772 (2007)

    PubMed  CAS  Article  Google Scholar 

  98. 98.

    D. Dingar, F. Konecny, J. Zou, X. Sun, R. von Harsdorf, Anti-apoptotic function of the E2F transcription factor 4 (E2F4)/p130, a member of retinoblastoma gene family in cardiac myocytes. J Mol Cell Cardiol 53, 820–828 (2007)

    Article  CAS  Google Scholar 

  99. 99.

    L. Zhao, M. Tang, Z. Hu, B. Yan, W. Pi, Z. Li, J. Zhang, L. Zhang, W. Jiang, G. Li, Y. Qiu, F. Hu, F. Liu, J. Lu, X. Chen, L. Xiao, Z. Xu, Y. Tao, L. Yang, A.M. Bode, Z. Dong, J. Zhou, J. Fan, L. Sun, & Cao Y. miR-504 mediated down-regulation of nuclear respiratory factor 1 leads to radio-resistance in nasopharyngeal carcinoma. Oncotarget 6, 15995–16018 (2015)

    PubMed  PubMed Central  Google Scholar 

  100. 100.

    R.B. Penney, D. Roy, Thioredoxin-mediated redox regulation of resistance to endocrine therapy in breast cancer. Biochim Biophys Acta 1836, 60–79 (2013)

    PubMed  CAS  Google Scholar 

  101. 101.

    B.N. Radde, M.M. Ivanova, H.X. Mai, N. Alizadeh-Rad, K. Piell, P. Van Hoose, M.P. Cole, P. Muluhngwi, T.S. Kalbfleisch, E.C. Rouchka, B.G. Hill, C.M. Klinge, Nuclear respiratory factor-1 and bioenergetics in tamoxifen-resistant breast cancer cells. Exp Cell Res 347, 222–231 (2016)

    PubMed  PubMed Central  CAS  Article  Google Scholar 

  102. 102.

    G. Zhang, D.T. Frederick, L. Wu, Z. Wei, C. Krepler, S. Srinivasan, Y.C. Chae, X. Xu, H. Choi, E. Dimwamwa, O. Ope, B. Shannan, D. Basu, D. Zhang, M. Guha, M. Xiao, S. Randell, K. Sproesser, W. Xu, J. Liu, G.C. Karakousis, L.M. Schuchter, T.C. Gangadhar, R.K. Amaravadi, M. Gu, C. Xu, A. Ghosh, W. Xu, T. Tian, J. Zhang, S. Zha, Q. Liu, P. Brafford, A. Weeraratna, M.A. Davies, J.A. Wargo, N.G. Avadhani, Y. Lu, G.B. Mills, D.C. Altieri, K.T. Flaherty, M. Herlyn, Targeting mitochondrial biogenesis to overcome drug resistance to MAPK inhibitors. J Clin Invest 126, 1834–1856 (2016)

    PubMed  PubMed Central  Article  Google Scholar 

  103. 103.

    M.H. Uddin, B. Kim, D.H. Suh, Y.S. Song, Anticancer strategy targeting mitochondrial biogenesis in ovarian Cancer. J Cancer Sci Therapy 6, 422–428 (2014)

    CAS  Article  Google Scholar 

  104. 104.

    A. Shen, L. Wang, M. Huang, J. Sun, Y. Chen, Y.Y. Shen, X. Yang, X. Wang, J. Ding, M. Geng, C-Myc alterations confer therapeutic response and acquired resistance to c-met inhibitors in MET-addicted cancers. Cancer Res 75, 4548–4559 (2015)

    PubMed  CAS  Article  Google Scholar 

  105. 105.

    X.N. Pan, J.J. Chen, L.X. Wang, R.Z. Xiao, L.L. Liu, Z.G. Fang, Q. Liu, Z.J. Long, D.J. Lin, Inhibition of c-Myc overcomes cytotoxic drug resistance in acute myeloid leukemia cells by promoting differentiation. PLoS One 9, e105381 (2014)

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  106. 106.

    L.H. Yan, X.T. Wang, J. Yang, F.B. Kong, C. Lian, W.Y. Wei, W. Luo, Y.B. Xie, Q. Xiao, Reversal of multidrug resistance in gastric cancer cells by E2F-1 downregulation in vitro and in vivo. J Cell Biochem 115, 34–41 (2014)

    PubMed  CAS  Article  Google Scholar 

  107. 107.

    M.T. Rosenfeldt, L.A. Bell, J.S. Long, J. O'Prey, C. Nixon, F. Roberts, C. Dufès, K.M. Ryan, E2F1 drives chemotherapeutic drug resistance via ABCG2. Oncogene 33, 4164–4172 (2014)

    PubMed  CAS  Article  Google Scholar 

  108. 108.

    J.J. Stevens, B. Graham, E. Dugo, B. Berhaneselassie-Sumner, K. Ndebele, P.B. Tchounwou, Arsenic trioxide induces apoptosis via specific signaling pathways in HT-29 colon cancer cells. J Cancer Sci Therapy 9, 298–306 (2017)

    Article  CAS  Google Scholar 

  109. 109.

    J.B. Bell, F. Eckerdt, H.D. Dhruv, D. Finlay, S. Peng, S. Kim, B. Kroczynska, E.M. Beauchamp, K. Alley, J. Clymer, S. Goldman, S.Y. Cheng, C.D. James, I. Nakano, C. Horbinski, A.P. Mazar, K. Vuori, P. Kumthekar, J. Raizer, M.E. Berens, L.C. Platanias, Differential response of glioma stem cells to arsenic trioxide therapy is regulated by MNK1 and mRNA translation. Mol Cancer Res 16, 32–46 (2018)

    PubMed  CAS  Article  Google Scholar 

  110. 110.

    F. Morrish, C. Giedt, D. Hockenbery, c-MYC apoptotic function is mediated by target genes. Genes Dev 17, 240–255 (2003)

    PubMed  PubMed Central  CAS  Article  Google Scholar 

  111. 111.

    Z. Li et al., The degradation of EZH2 mediated by lncRNA ANCR attenuated the invasion and metastasis of breast cancer. Cell Death Diff 24, 59–71 (2017)

    Article  CAS  Google Scholar 

  112. 112.

    H. Kurihara, R. Maruyama, K. Ishiguro, S. Kanno, I. Yamamoto, K. Ishigami, K. Mitsuhashi, H. Igarashi, M. Ito, T. Tanuma, Y. Sukawa, K. Okita, T. Hasegawa, K. Imai, H. Yamamoto, Y. Shinomura, K. Nosho, The relationship between EZH2 expression and microRNA-31 in colorectal cancer and the role in evolution of the serrated pathway. Oncotarget 7, 12704–12717 (2016)

    PubMed  PubMed Central  Article  Google Scholar 

  113. 113.

    A.P. Russell, S. Lamon, H. Boon, S. Wada, I. Güller, E.L. Brown, A.V. Chibalin, J.R. Zierath, R.J. Snow, N. Stepto, G.D. Wadley, T. Akimoto, Regulation of miRNAs in human skeletal muscle following acute endurance exercise and short-term endurance training. J Physiol 591, 4637–4653 (2013)

    PubMed  PubMed Central  CAS  Article  Google Scholar 

  114. 114.

    B. Kunkle, Q. Felty, G. Narasimhan, F. Trevino, D. Roy. Meta-analysis of brain tumor microarray data using Oncomine identifies NRF1, TFAM and MYC co-expressed genes: Its implications in the development of childhood brain tumors. 18th World IMACS / MODSIM Congress, Cairns, Australia 720–726 (2009)

  115. 115.

    W.R. Taylor, A.H. Schonthal, J. Galante, G.R. Stark, p130/E2F4 binds to and represses the cdc2 promoter in response to p53. J Biol Chem 276, 1998–2006 (2001)

    PubMed  CAS  Article  Google Scholar 

  116. 116.

    T.L. Born, J.A. Frost, A. Schönthal, G.C. Prendergast, J.R. Feramisco, C-Myc cooperates with activated Ras to induce the cdc2 promoter. Mol Cell Biol 14, 5710–5718 (1994)

    PubMed  PubMed Central  CAS  Article  Google Scholar 

  117. 117.

    I.B. Rosenwald, D.B. Rhoads, L.D. Callanan, K.J. Isselbacher, E.V. Schmidt, Increased expression of eukaryotic translation initiation factors eIF-4E and eIF-2a in response to growth induction by c-myc. Proc Natl Acad Sci U S A 90, 6175–6178 (1993)

    PubMed  PubMed Central  CAS  Article  Google Scholar 

  118. 118.

    V.O. Okoh, Q. Felty, J. Parkash, R. Poppiti, D. Roy, Reactive oxygen species via redox signaling to PI3K/AKT pathway contribute to the malignant growth of 4-hydroxy estradiol-transformed mammary epithelial cells. PLoS One 8, e54206 (2013)

    PubMed  PubMed Central  CAS  Article  Google Scholar 

  119. 119.

    M.V. Oli, M.M. Grober, G. Giurato, M. Ravo, L. Cicatiello, M.R.D. Filippo, L. Ferraro, G. Nassa, M.F. Papa, O. Paris, R. Tarallo, S. Luo, G.P. Schroth, V.B.A. Weisz, Global analysis of estrogen receptor beta binding to breast cancer cell genome reveals an extensive interplay with estrogen receptor alpha for target gene regulation. BMC Genomics 12, 1471–2164 (2011)

    Google Scholar 

  120. 120.

    I. Riz, R.G. Hawley, G1/S transcriptional networks modulated by the HOX11/TLX1 oncogene of T-cell acute lymphoblastic leukemia. Oncogene 24, 5561–5575 (2005)

    PubMed  PubMed Central  CAS  Article  Google Scholar 

  121. 121.

    R. Tongbai, G. Idelman, S.H. Nordgard, W. Cui, J.L. Jacobs, C.M. Haggerty, S.J. Chanock, A.L. Borrensen-Dale, G. Livingston, P. Shaunessy, C.H. Chiang, V.N. Kristensen, S. Bilke, K. Gardner, Transcriptional networks inferred from molecular signatures of breast cancer. Am J Pathol 172, 495–509 (2008)

    PubMed  PubMed Central  CAS  Article  Google Scholar 

  122. 122.

    F. Li, Y. Wang, K.I. Zeller, J.J. Potter, D.R. Wonsey, K.A. O’Donnell, J.W. Kim, J.T. Yustein, L.A. Lee, C.V. Dang, Myc stimulates nuclearly encoded mitochondrial genes and mitochondrial biogenesis. Mol Cell Biol 25, 6225–6234 (2005)

    PubMed  PubMed Central  CAS  Article  Google Scholar 

  123. 123.

    R. Elkon, K.I. Zeller, C. Linhart, C.V. Dang, R. Shamir, Y. Shiloh, In silico identification of transcriptional regulators associated with c-Myc. Nucleic Acids Res 32, 4955–4961 (2004)

    PubMed  PubMed Central  CAS  Article  Google Scholar 

  124. 124.

    M. Collu-Marchese, M. Shuen, M. Pauly, A. Saleem, D.A. Hood, The regulation of mitochondrial transcription factor a (Tfam) expression during skeletal muscle cell differentiation. Biosci Rep 35, e00221 (2015)

    PubMed  PubMed Central  Google Scholar 

  125. 125.

    M. Lynch, L. Chen, M.J. Ravitz, S. Mehtani, K. Korenblat, M.J. Pazin, E.V. Schmidt, hnRNP K binds a core polypyrimidine element in the eukaryotic translation initiation factor 4E (eIF4) promoter, and its regulation of eIF4E contributes to neoplastic transformation. Mol Cell Biol 25, 6436–6453 (2005)

    PubMed  PubMed Central  CAS  Article  Google Scholar 

  126. 126.

    L. Zhang, H. Yu, P. Wang, Q. Ding, Z. Wang, Screening of transcription factors with transcriptional initiation activity. Gene 531, 64–70 (2013)

    PubMed  CAS  Article  Google Scholar 

  127. 127.

    W. Mao, D. Kostka, M. Chikina, Modeling enhancer-promoter interactions with attention-based neural networks bioRxiv (2017). https://doi.org/10.1101/219667

  128. 128.

    S. Mahara, W.J. Chng, Q. Yu, Molecular switch of EZH2 in hypoxia. Cell Cycle 15, 3007–3008 (2016)

    PubMed  PubMed Central  CAS  Article  Google Scholar 

  129. 129.

    M.R. Doe, J.M. Ascano, M. Kaur, M.D. Cole, Myc posttranscriptionally induces HIF1 protein and target gene expression in normal and cancer cells. Cancer Res 72, 949–957 (2012)

    PubMed  CAS  Article  Google Scholar 

  130. 130.

    B.-K. Lee, A.A. Bhinge, V.R. Iyer, Wide-ranging functions of E2F4 in transcriptional activation and repression revealed by genome-wide analysis. Nucleic Acids Res 39, 3558–3573 (2011)

    PubMed  PubMed Central  CAS  Article  Google Scholar 

  131. 131.

    S. Terry, S. Buart, T.Z. Tan, G. Gros, M.Z. Noman, J.B. Lorens, F. Mami-Chouaib, J.P. Thiery, S. Chouaib, Acquisition of tumor cell phenotypic diversity along the EMT spectrum under hypoxic pressure: Consequences on susceptibility to cell-mediated cytotoxicity. OncoImmunology 6, 2 (2017)

    Article  CAS  Google Scholar 

  132. 132.

    S. Moniz, D. Bandarra, J. Biddlestone, K.J. Campbell, D. Komander, A. Bremm, S. Rocha, Cezanne regulates E2F1-dependent HIF2α expression. J Cell Sci 128, 3082–3093 (2015)

    PubMed  PubMed Central  CAS  Article  Google Scholar 

  133. 133.

    S.T. Shors, J.S.E. Bassey, S.J. Harkin, B. Safer, Formation of alpha-pal/max heterodimers synergistically activates the eIF2-alpha promoter. J Biol Chem 273, 34703–34709 (1998)

    PubMed  CAS  Article  Google Scholar 

  134. 134.

    D. Kumari, A. Gabrielian, D. Wheeler, K. Usdin, The roles of Sp1, Sp3, USF1/USF2 and NRF-1 in the regulation and three-dimensional structure of the fragile X mental retardation gene promoter. Biochem J 386, 297–303 (2005)

    PubMed  PubMed Central  CAS  Article  Google Scholar 

  135. 135.

    D.E. Fisher, L.A. Parent, P.A. Sharp, Myc/max and other helix-loop-helix/leucine zipper proteins bend DNA toward the minor groove. Proc Natl Acad Sci U S A 89, 11779–11783 (1992)

    PubMed  PubMed Central  CAS  Article  Google Scholar 

Download references

Acknowledgments

This work was, in part, supported by a VA MERIT Review (VA BX001463) grant to DR.

Author information

Affiliations

Authors

Corresponding author

Correspondence to Deodutta Roy.

Ethics declarations

Conflict of interest

None declared.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Bhawe, K., Roy, D. Interplay between NRF1, E2F4 and MYC transcription factors regulating common target genes contributes to cancer development and progression. Cell Oncol. 41, 465–484 (2018). https://doi.org/10.1007/s13402-018-0395-3

Download citation

Keywords

  • Nuclear respiratory factor 1 (NRF1)
  • E2F4
  • MYC
  • Cancer