Role of Sp1 in Liver Cancer

  • Himanshu Tillu
  • Pallaval Veera BramhachariEmail author


Liver cancer is one of the most serious public health concerns in the world with unhealthy lifestyle and infection with oncogenic viruses contributing to tumorigenesis. Hepatocellular carcinoma (HCC) which originates from the hepatocytes is the most ubiquitous form of liver cancer and is the sixth most prevalent cancer globally. The specificity protein 1 (Sp1) transcription factor occupies an important functional niche in varied cellular processes including cell division, differentiation, cell adhesion, immune response, apoptosis, chromatin remodeling, and DNA damage response. Considering the central position of Sp1 in the life cycle of cells, it is conceivable that Sp1 could be intimately associated with the process of transformation. Some of the pharmacological agents exert their antineoplastic effects through the inhibition of Sp1 response, thereby underlining the importance of Sp1 in the process of carcinogenesis. Over the years, evidence has built up implicating the role of Sp1 in various features of tumorigenesis including proliferation of cancerous cells, cell cycle regulation, invasion and metastasis, angiogenesis, and apoptosis. This review evaluates the contributions of Sp1 to various aspects of HCC.


Hepatocellular carcinoma (HCC) Specificity protein (Sp1) Hepatitis C virus (HCV) Liver cancer Hepatitis B virus (HBV) 


  1. 1.
    Abdelrahim M, Samudio I et al (2002) Small inhibitory RNA duplexes for Sp1 mRNA block basal and estrogen-induced gene expression and cell cycle progression in MCF-7 breast cancer cells. J Biol Chem 277(32):28815–28822CrossRefPubMedGoogle Scholar
  2. 2.
    Abedin M, King N (2010) Diverse evolutionary paths to cell adhesion. Trends Cell Biol 20(12):734–742PubMedPubMedCentralCrossRefGoogle Scholar
  3. 3.
    Adhikary S, Marinoni F, Hock A, Hulleman E et al (2005) The ubiquitin ligase HectH9 regulates transcriptional activation by Myc and is essential for tumor cell proliferation. Cell 123(3):409–421PubMedCrossRefGoogle Scholar
  4. 4.
    Asselin C, Nepveu A et al (1989) Molecular requirements for transcriptional initiation of the murine c-myc gene. Oncogene 4(5):549–558PubMedPubMedCentralGoogle Scholar
  5. 5.
    Bakiri L, Wagner EF (2013) Mouse models for liver cancer. Mol Oncol 7(2):206–223PubMedPubMedCentralCrossRefGoogle Scholar
  6. 6.
    Beishline K, Azizkhan-Clifford J (2015) Sp1 and the ‘hallmarks of cancer’. FEBS J 282(2):224–258PubMedPubMedCentralCrossRefGoogle Scholar
  7. 7.
    Carrano AC, Eytan E, Hershko A et al (1999) SKP2 is required for ubiquitin-mediated degradation of the CDK inhibitor p27. Nat Cell Biol 1(4):193–199PubMedCrossRefGoogle Scholar
  8. 8.
    Caviglia JM, Schwabe RF (2015) Mouse models of liver cancer. Methods Mol Biol 1267:165–183PubMedCrossRefGoogle Scholar
  9. 9.
    Center for Disease Control and Prevention (CDC) (2017) Liver Cancer. Available online at
  10. 10.
    Chang HC, Liu LT et al (2004) Involvement of histone deacetylation in ras-induced down-regulation of the metastasis suppressor RECK. Cell Signal 16(6):675–679PubMedCrossRefGoogle Scholar
  11. 11.
    Chen J, Wu FX et al (2016) Berberine upregulates miR-22-3p to suppress hepatocellular carcinoma cell proliferation by targeting Sp1. Am J Transl Res 8(11):4932–4941PubMedPubMedCentralGoogle Scholar
  12. 12.
    Chen JS, Su IJ et al (2012) Expression of T-cell lymphoma invasion and metastasis 2 (TIAM2) promotes proliferation and invasion of liver cancer. Int J Cancer 130(6):1302–1313PubMedCrossRefGoogle Scholar
  13. 13.
    Chung SK, Kim JY, Lim JY et al (2011) Transcription factor sp1 is involved in expressional regulation of coxsackie and adenovirus receptor in cancer cells. BioMed Res Int 2011:636497Google Scholar
  14. 14.
    DeGregori J (2002) The genetics of the E2F family of transcription factors: shared functions and unique roles. Biochim Biophys Acta 1602(2):131–150PubMedPubMedCentralGoogle Scholar
  15. 15.
    Donovan K, Alekseev O, Qi X et al (2014) O-GlcNAc modification of transcription factor Sp1 mediates hyperglycemia-induced VEGF-A upregulation in retinal cells Sp1 O-GlcNAcylation upregulates VEGF-A. Invest Ophthalmol Vis Sci 55(12):7862–7873PubMedPubMedCentralCrossRefGoogle Scholar
  16. 16.
    Eisermann K, Broderick CJ, Bazarov A et al (2013) Androgen up-regulates vascular endothelial growth factor expression in prostate cancer cells via an Sp1 binding site. Mol Cancer 12(1):7PubMedPubMedCentralCrossRefGoogle Scholar
  17. 17.
    Fatehullah A, Tan SH et al (2016) Organoids as an in vitro model of human development and disease. Nat Cell Biol 18(3):246–254PubMedCrossRefPubMedCentralGoogle Scholar
  18. 18.
    Finkenzeller G, Sparacio A et al (1997) Sp1 recognition sites in the proximal promoter of the human vascular endothelial growth factor gene are essential for platelet-derived growth factor-induced gene expression. Oncogene 15(6):669–676CrossRefPubMedGoogle Scholar
  19. 19.
    Furumoto K, Arii S et al (2001) RECK gene expression in hepatocellular carcinoma: correlation with invasion-related clinicopathological factors and its clinical significance. Reverse-inducing – cysteine-rich protein with Kazal motifs. Hepatology 33(1):189–195PubMedCrossRefGoogle Scholar
  20. 20.
    Gandhy SU, Imanirad P et al (2015) Specificity protein (Sp) transcription factors and metformin regulate expression of the long non-coding RNA HULC. Oncotarget 6(28):26359–26372PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Gialeli C, Theocharis AD, Karamanos NK (2011) Roles of matrix metalloproteinases in cancer progression and their pharmacological targeting. FEBS J 278(1):16–27PubMedCrossRefGoogle Scholar
  22. 22.
    Gidoni D, Kadonaga JT et al (1985) Bidirectional SV40 transcription mediated by tandem Sp1 binding interactions. Science 230(4725):511–517PubMedCrossRefGoogle Scholar
  23. 23.
    Giglioni B, Comi P et al (1989) The same nuclear proteins bind the proximal CACCC box of the human beta-globin promoter and a similar sequence in the enhancer. Biochem Biophys Res Commun 164(1):149–155PubMedCrossRefGoogle Scholar
  24. 24.
    Grinstein E, Jundt F, Weinert I et al (2002) Sp1 as G1 cell cycle phase specific transcription factor in epithelial cells. Oncogene 21(10):1485CrossRefPubMedGoogle Scholar
  25. 25.
    Guan H, Cai J, Zhang N et al (2012) Sp1 is upregulated in human glioma, promotes MMP-2-mediated cell invasion and predicts poor clinical outcome. Int J Cancer 130(3):593–601PubMedCrossRefGoogle Scholar
  26. 26.
    Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100(1):57–70PubMedPubMedCentralCrossRefGoogle Scholar
  27. 27.
    Hsu MC, Chang HC et al (2006) HER-2/neu represses the metastasis suppressor RECK via ERK and Sp transcription factors to promote cell invasion. J Biol Chem 281(8):4718–4725PubMedCrossRefGoogle Scholar
  28. 28.
    Hung WC, Tseng WL et al (2010) Skp2 overexpression increases the expression of MMP-2 and MMP-9 and invasion of lung cancer cells. Cancer Lett 288(2):156–161PubMedCrossRefGoogle Scholar
  29. 29.
    Iqbal J, McRae S et al (2013) Mechanism of hepatitis C virus (HCV)-induced osteopontin and its role in epithelial to mesenchymal transition of hepatocytes. J Biol Chem 288(52):36994–37009PubMedPubMedCentralCrossRefGoogle Scholar
  30. 30.
    Jensen DE, Black AR et al (1997) Distinct roles for Sp1 and E2F sites in the growth/cell cycle regulation of the DHFR promoter. J Cell Biochem 67(1):24–31PubMedPubMedCentralCrossRefGoogle Scholar
  31. 31.
    Kieran MW, Kalluri R et al (2012) The VEGF pathway in cancer and disease: responses, resistance, and the path forward. Cold Spring Harb Perspect Med 2(12):a006593PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Kim JY, Kim EH et al (2008) Quercetin sensitizes human hepatoma cells to TRAIL-induced apoptosis via Sp1-mediated DR5 up-regulation and proteasome-mediated c-FLIPS down-regulation. J Cell Biochem 105(6):1386–1398PubMedCrossRefGoogle Scholar
  33. 33.
    Kim NW, Piatyszek MA et al (1994) Specific association of human telomerase activity with immortal cells and cancer. Science 266(5193):2011–2015PubMedCrossRefGoogle Scholar
  34. 34.
    Kong LM, Liao CG, Chen L et al (2011) Promoter hypomethylation up-regulates CD147 expression through increasing Sp1 binding and associates with poor prognosis in human hepatocellular carcinoma. J Cell Mol Med 15(6):1415–1428PubMedCrossRefGoogle Scholar
  35. 35.
    Kong LM, Yao L et al (2016) Interaction of KLF6 and Sp1 regulates basigin-2 expression mediated proliferation, invasion and metastasis in hepatocellular carcinoma. Oncotarget 7(19):27975–27987PubMedPubMedCentralGoogle Scholar
  36. 36.
    Koos RD, Kazi AA et al (2005) New insight into the transcriptional regulation of vascular endothelial growth factor expression in the endometrium by estrogen and relaxin. Ann N Y Acad Sci 1041:233–247PubMedCrossRefGoogle Scholar
  37. 37.
    Kumar AP, Butler AP (1998) Serum responsive gene expression mediated by Sp1. Biochem Biophys Res Commun 252(2):517–523CrossRefPubMedGoogle Scholar
  38. 38.
    Kuo L, Chang HC et al (2006) Src oncogene activates MMP-2 expression via the ERK/Sp1 pathway. J Cell Physiol 207(3):729–734PubMedCrossRefGoogle Scholar
  39. 39.
    Kutoh E, Margot JB et al (1999) Identification and characterization of the putative retinoblastoma control element of the rat insulin-like growth factor binding protein-2 gene. Cancer Lett 136(2):187–194CrossRefPubMedGoogle Scholar
  40. 40.
    Lee S, Park U et al (2001) Hepatitis C virus core protein transactivates insulin-like growth factor II gene transcription through acting concurrently on Egr1 and Sp1 sites. Virology 283(2):167–177PubMedCrossRefGoogle Scholar
  41. 41.
    Lee YI, Lee S et al (1998) The human hepatitis B virus transactivator X gene product regulates Sp1 mediated transcription of an insulin-like growth factor II promoter 4. Oncogene 16(18):2367–2380PubMedCrossRefGoogle Scholar
  42. 42.
    Li J, Ou JH (2001) Differential regulation of hepatitis B virus gene expression by the Sp1 transcription factor. J Virol 75(18):8400–8406PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Liao CG, Kong LM et al (2011) Characterization of basigin isoforms and the inhibitory function of basigin-3 in human hepatocellular carcinoma proliferation and invasion. Mol Cell Biol 31(13):2591–2604PubMedPubMedCentralCrossRefGoogle Scholar
  44. 44.
    Lin Y, Ye JZ, Yan XX et al (2016) High expression of Sp1 is significantly correlated with tumor progression and poor prognosis in patients with hepatocellular carcinoma. Int J Clin Exp Pathol 9(10):10373–10381Google Scholar
  45. 45.
    Liu H, Shi W et al (2010) Hepatitis B virus X protein upregulates transcriptional activation of human telomerase reverse transcriptase. Virus Genes 40(2):174–182PubMedCrossRefGoogle Scholar
  46. 46.
    Liu N, Ding D et al (2016) hTERT promotes tumor angiogenesis by activating VEGF via interactions with the Sp1 transcription factor. Nucleic Acids Res 44(18):8693–8703PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    Ma Z, Chang MJ, Shah R et al (2004) Brg-1 is required for maximal transcription of the human matrix metalloproteinase-2 gene. J Biol Chem 279(44):46326–46334PubMedCrossRefGoogle Scholar
  48. 48.
    Ming-de Huang WMC, Qi FZ, Xia R et al (2015) Long non-coding RNA ANRIL is upregulated in hepatocellular carcinoma and regulates cell apoptosis by epigenetic silencing of KLF2. J Hematol Oncol 8:50PubMedCrossRefGoogle Scholar
  49. 49.
    Moon DO, Kang CH et al (2012) Capsaicin sensitizes TRAIL-induced apoptosis through Sp1-mediated DR5 up-regulation: involvement of Ca(2+) influx. Toxicol Appl Pharmacol 259(1):87–95PubMedCrossRefGoogle Scholar
  50. 50.
    Mukozu T, Nagai H et al (2013) Serum VEGF as a tumor marker in patients with HCV-related liver cirrhosis and hepatocellular carcinoma. Anticancer Res 33(3):1013–1021PubMedPubMedCentralGoogle Scholar
  51. 51.
    Muto Y, Moriwaki H et al (1999) Prevention of second primary tumors by an acyclic retinoid in patients with hepatocellular carcinoma. N Engl J Med 340(13):1046–1047PubMedCrossRefGoogle Scholar
  52. 52.
    Nam EH, Lee Y, Park YK et al (2012) ZEB2 upregulates integrin α5 expression through cooperation with Sp1 to induce invasion during epithelial–mesenchymal transition of human cancer cells. Carcinogenesis 33:563–571. bgs005PubMedCrossRefGoogle Scholar
  53. 53.
    Nart D, Yaman B et al (2010) Expression of matrix metalloproteinase-9 in predicting prognosis of hepatocellular carcinoma after liver transplantation. Liver Transpl 16(5):621–630PubMedPubMedCentralGoogle Scholar
  54. 54.
    Noe V, Chen C et al (1997) Cell-growth regulation of the hamster dihydrofolate reductase gene promoter by transcription factor Sp1. Eur J Biochem 249(1):13–20CrossRefPubMedGoogle Scholar
  55. 55.
    Noh JH, Jung KH et al (2011) Aberrant regulation of HDAC2 mediates proliferation of hepatocellular carcinoma cells by deregulating expression of G1/S cell cycle proteins. PLoS One 6(11):e28103PubMedPubMedCentralCrossRefGoogle Scholar
  56. 56.
    Oster SK, Ho CS et al (2002) The myc oncogene: marvelously complex. Adv Cancer Res 84:81–154PubMedCrossRefGoogle Scholar
  57. 57.
    Pagès G, Pouysségur J (2005) Transcriptional regulation of the vascular endothelial growth factor gene–a concert of activating factors. Cardiovasc Res 65(3):564–573PubMedCrossRefGoogle Scholar
  58. 58.
    Pal S, Claffey KP et al (1998) Activation of Sp1-mediated vascular permeability factor/vascular endothelial growth factor transcription requires specific interaction with protein kinase C zeta. J Biol Chem 273(41):26277–26280PubMedCrossRefGoogle Scholar
  59. 59.
    Pan X, Wang H et al (2016) Physcion induces apoptosis in hepatocellular carcinoma by modulating miR-370. Am J Cancer Res 6(12):2919–2931PubMedPubMedCentralGoogle Scholar
  60. 60.
    Peng H, Li Y et al (2017) HBx and SP1 upregulate DKK1 expression. Acta Biochim Pol 64(1):35–39PubMedCrossRefGoogle Scholar
  61. 61.
    Pore N, Liu S, Shu HK et al (2004) Sp1 is involved in Akt-mediated induction of VEGF expression through an HIF-1–independent mechanism. Mol Biol Cell 15(11):4841–4853PubMedPubMedCentralCrossRefGoogle Scholar
  62. 62.
    Presser LD, McRae S et al (2013) Activation of TGF-beta1 promoter by hepatitis C virus-induced AP-1 and Sp1: role of TGF-beta1 in hepatic stellate cell activation and invasion. PLoS One 8(2):e56367PubMedPubMedCentralCrossRefGoogle Scholar
  63. 63.
    Qin H, Sun Y et al (1999) The transcription factors Sp1, Sp3, and AP-2 are required for constitutive matrix metalloproteinase-2 gene expression in astroglioma cells. J Biol Chem 274(41):29130–29137CrossRefPubMedGoogle Scholar
  64. 64.
    Raney AK, McLachlan A (1995) Characterization of the hepatitis B virus large surface antigen promoter Sp1 binding site. Virology 208(1):399–404PubMedCrossRefGoogle Scholar
  65. 65.
    Raney AK, Le HB et al (1992) Regulation of transcription from the hepatitis B virus major surface antigen promoter by the Sp1 transcription factor. J Virol 66(12):6912–6921PubMedPubMedCentralGoogle Scholar
  66. 66.
    Reisinger K, Kaufmann R et al (2003) Increased Sp1 phosphorylation as a mechanism of hepatocyte growth factor (HGF/SF)-induced vascular endothelial growth factor (VEGF/VPF) transcription. J Cell Sci 116(Pt 2):225–238PubMedCrossRefGoogle Scholar
  67. 67.
    Safe S, Abdelrahim M (2005) Sp transcription factor family and its role in cancer. Eur J Cancer 41(16):2438–2448PubMedPubMedCentralCrossRefGoogle Scholar
  68. 68.
    Saito M, Kohara M et al (2012) Hepatitis C virus promotes expression of the 3beta-hydroxysterol delta24-reductase through Sp1. J Med Virol 84(5):733–746PubMedCrossRefGoogle Scholar
  69. 69.
    Sasahara RM, Takahashi C et al (1999) Involvement of the Sp1 site in ras-mediated downregulation of the RECK metastasis suppressor gene. Biochem Biophys Res Commun 264(3):668–675PubMedCrossRefGoogle Scholar
  70. 70.
    Schafer G, Cramer T et al (2003) Oxidative stress regulates vascular endothelial growth factor-A gene transcription through Sp1- and Sp3-dependent activation of two proximal GC-rich promoter elements. J Biol Chem 278(10):8190–8198PubMedCrossRefGoogle Scholar
  71. 71.
    Schafer KA (1998) The cell cycle: a review. Vet Pathol 35(6):461–478PubMedPubMedCentralCrossRefGoogle Scholar
  72. 72.
    Schilling LJ, Farnham PJ (1995) The bidirectionally transcribed dihydrofolate reductase and rep-3a promoters are growth regulated by distinct mechanisms. Cell Growth Differ 6(5):541–548PubMedGoogle Scholar
  73. 73.
    Sherr CJ, Roberts JM (2004) Living with or without cyclins and cyclin-dependent kinases. Genes Dev 18(22):2699–2711PubMedCrossRefGoogle Scholar
  74. 74.
    Sherr CJ, Roberts JM (1999) CDK inhibitors: positive and negative regulators of G1-phase progression. Genes Dev 13(12):1501–1512PubMedCrossRefGoogle Scholar
  75. 75.
    Shibuya M (2013) Vascular endothelial growth factor and its receptor system: physiological functions in angiogenesis and pathological roles in various diseases. J Biochem 153(1):13–19PubMedCrossRefGoogle Scholar
  76. 76.
    Snyder RC, Ray R et al (1991) Mithramycin blocks transcriptional initiation of the c-myc P1 and P2 promoters. Biochemistry 30(17):4290–4297PubMedCrossRefGoogle Scholar
  77. 77.
    Sorensen P, Wintersberger E (1999) Sp1 and NF-Y are necessary and sufficient for growth-dependent regulation of the hamster thymidine kinase promoter. J Biol Chem 274(43):30943–30949PubMedPubMedCentralCrossRefGoogle Scholar
  78. 78.
    Spencer JA, Major ML et al (1999) Basic fibroblast growth factor activates serum response factor gene expression by multiple distinct signaling mechanisms. Mol Cell Biol 19(6):3977–3988PubMedPubMedCentralCrossRefGoogle Scholar
  79. 79.
    Stoner M, Wormke M, Saville B, Samudio I, Qin C, Abdelrahim M, Safe S (2004) Estrogen regulation of vascular endothelial growth factor gene expression in ZR-75 breast cancer cells through interaction of estrogen receptor α and SP proteins. Oncogene, 23(5):1052–1063CrossRefGoogle Scholar
  80. 80.
    Sun Y, Xun K et al (2009) A systematic review of the anticancer properties of berberine, a natural product from Chinese herbs. Anti-Cancer Drugs 20(9):757–769PubMedCrossRefGoogle Scholar
  81. 81.
    Sutterluty H, Chatelain E et al (1999) p45SKP2 promotes p27Kip1 degradation and induces S phase in quiescent cells. Nat Cell Biol 1(4):207–214PubMedCrossRefGoogle Scholar
  82. 82.
    Sze KMF, Wong KLT, Chu GKY et al (2011) Loss of phosphatase and tensin homolog enhances cell invasion and migration through aKT/Sp-1 transcription factor/matrix metalloproteinase 2 activation in hepatocellular carcinoma and has clinicopathologic significance. Hepatology 53(5):1558–1569PubMedCrossRefGoogle Scholar
  83. 83.
    Tao YM, Liu Z et al (2013) Dickkopf-1 (DKK1) promotes invasion and metastasis of hepatocellular carcinoma. Dig Liver Dis 45(3):251–257PubMedCrossRefGoogle Scholar
  84. 84.
    Tatsukawa H, Sano T et al (2011) Dual induction of caspase 3- and transglutaminase-dependent apoptosis by acyclic retinoid in hepatocellular carcinoma cells. Mol Cancer 10:4PubMedPubMedCentralCrossRefGoogle Scholar
  85. 85.
    Tischer E, Mitchell R et al (1991) The human gene for vascular endothelial growth factor. Multiple protein forms are encoded through alternative exon splicing. J Biol Chem 266(18):11947–11954PubMedPubMedCentralGoogle Scholar
  86. 86.
    Tsukiyama-Kohara K (2012) Role of oxidative stress in hepatocarcinogenesis induced by hepatitis C virus. Int J Mol Sci 13(11):15271–15278PubMedPubMedCentralCrossRefGoogle Scholar
  87. 87.
    Tu CC, Kumar VB et al (2013) Estrogen receptor alpha (ESR1) over-expression mediated apoptosis in Hep3B cells by binding with SP1 proteins. J Mol Endocrinol 51(1):203–212PubMedCrossRefGoogle Scholar
  88. 88.
    Wai Wong C, Dye DE et al (2012) The role of immunoglobulin superfamily cell adhesion molecules in cancer metastasis. Int J Cell Biol 2012:340296PubMedPubMedCentralCrossRefGoogle Scholar
  89. 89.
    Wang J, Liu X, Ni P et al (2010) SP1 is required for basal activation and chromatin accessibility of CD151 promoter in liver cancer cells. Biochem Biophys Res Commun 393(2):291–296PubMedCrossRefGoogle Scholar
  90. 90.
    Wang W, Cheng J, Qin JJ et al (2014) RYBP expression is associated with better survival of patients with hepatocellular carcinoma (HCC) and responsiveness to chemotherapy of HCC cells in vitro and in vivo. Oncotarget 5(22):11604–11619PubMedPubMedCentralGoogle Scholar
  91. 91.
    Wang CH, Chang HC et al (2006) p16 inhibits matrix metalloproteinase-2 expression via suppression of Sp1-mediated gene transcription. J Cell Physiol 208(1):246–252PubMedCrossRefGoogle Scholar
  92. 92.
    Wang L, Guan X et al (2005) Altered expression of transcription factor Sp1 critically impacts the angiogenic phenotype of human gastric cancer. Clin Exp Metastasis 22(3):205–213PubMedCrossRefGoogle Scholar
  93. 93.
    Wierstra I, Alves J (2008) Cyclin E/Cdk2, P/CAF, and E1A regulate the transactivation of the c-myc promoter by FOXM1. Biochem Biophys Res Commun 368(1):107–115PubMedCrossRefGoogle Scholar
  94. 94.
    Yang CH, Yue J, Sims M et al (2013) The curcumin analog EF24 targets NF-κB and miRNA-21, and has potent anticancer activity in vitro and in vivo. PLoS One 8(8):71130CrossRefGoogle Scholar
  95. 95.
    Yang H, Huang ZZ et al (2001) The role of c-Myb and Sp1 in the up-regulation of methionine adenosyltransferase 2A gene expression in human hepatocellular carcinoma. FASEB J 15(9):1507–1516PubMedCrossRefGoogle Scholar
  96. 96.
    Yang Y, Zhang Y et al (2016) Discontinuation of anti-VEGF cancer therapy promotes metastasis through a liver revascularization mechanism. Nat Commun 7:12680PubMedPubMedCentralCrossRefGoogle Scholar
  97. 97.
    Yang ZF, Poon RT (2008) Vascular changes in hepatocellular carcinoma. Anat Rec (Hoboken) 291(6):721–734CrossRefGoogle Scholar
  98. 98.
    Yao M, Zhou W et al (2005) Effects of nonselective cyclooxygenase inhibition with low-dose ibuprofen on tumor growth, angiogenesis, metastasis, and survival in a mouse model of colorectal cancer. Clin Cancer Res 11(4):1618–1628PubMedCrossRefGoogle Scholar
  99. 99.
    Yuan P, Wang L et al (2007) Therapeutic inhibition of Sp1 expression in growing tumors by mithramycin a correlates directly with potent antiangiogenic effects on human pancreatic cancer. Cancer 110(12):2682–2690PubMedPubMedCentralCrossRefGoogle Scholar
  100. 100.
    Zhang H, Sun X, Ma L (2016) MicroRNA-1284 enhances radio-sensitivity in hepatocellular carcinoma cells by regulating SP1. Int J Clin Exp Pathol 9(11):11420–11427Google Scholar
  101. 101.
    Zhang G, Feng GY et al (2017) Correlation between liver cancer pain and the HIF-1 and VEGF expression levels. Oncol Lett 13(1):77–80PubMedCrossRefGoogle Scholar
  102. 102.
    Zhao Q, Cai W, Zhang X et al (2017) RYBP expression is regulated by KLF4 and Sp1 and is related to hepatocellular carcinoma prognosis. J Biol Chem 292(6):2143–2158PubMedCrossRefGoogle Scholar
  103. 103.
    Zhou JH, Zhang TT et al (2000) TIGAR contributes to ischemic tolerance induced by cerebral preconditioning through scavenging of reactive oxygen species and inhibition of apoptosis. Sci Rep 6:27096CrossRefGoogle Scholar
  104. 104.
    Zou S, Gu Z, Ni P, Liu X, Wang J, Fan Q (2012) SP1 plays a pivotal role for basal activity of TIGAR promoter in liver cancer cell lines. Mol cell biochem 359(1–2):17–23PubMedCrossRefGoogle Scholar

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© Springer Nature Singapore Pte Ltd 2017

Authors and Affiliations

  1. 1.Sysmex India Private LimitedMumbaiIndia
  2. 2.Department of BiotechnologyKrishna UniversityMachilipatnamIndia

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