HBx and SP1 upregulate DKK1 expression

• Authors: Hong Peng , Yongguo Li , Yunzhi Liu , Jingnan Zhang , Ke Chen , Ailong Huang , Hua Tang
• Languages of publication: EN

Abstracts

EN

Numerous evidences suggested that the hepatitis B virus (HBV) was recognized as an important factor in the development of hepatocellular carcinoma (HCC). Dickkopf-1 (DKK1) recently was reported to be involved in the progress of HCC. HBV may regulate DKK1 expression in hematoma carcinogenesis. Here, we demonstrated that HBV could regulate DKK1 promoter activity which resulted in upregulation of its mRNA and protein expression in several HBV existing cell lines, and HBx played a prominent role in this process. Transcription factor binding site search result showed that there is a SP1 site in DKK1 promoter region. Luciferase assay showed that overexpression of SP1 could increase DKK1 promoter activity in a dose dependent manner. Accordingly, siRNA inhibition of SP1 expression reduced DKK1 promoter activity and decreased the expression of DKK1 protein.

Keywords

EN

HCC; HBV; DKK1; SP1

• Publisher: Polish Biochemical Society
• Journal: Acta Biochimica Polonica
• Year: 2017
• Volume: 64
• Issue: 1
• Pages: 35-39

Dates

published

2017

received

2016-01-14

revised

2016-05-20

accepted

2016-07-13

(unknown)

2016-10-10

Contributors

author

Hong Peng

• Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, PR China

author

Yongguo Li

• Department of forensic medicine, Chongqing Medical University, Chongqing, 400016, China

author

Yunzhi Liu

• Department of forensic medicine, Chongqing Medical University, Chongqing, 400016, China

author

Jingnan Zhang

• Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, PR China

author

Ke Chen

• Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, PR China

author

Ailong Huang

• Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, PR China

author

Hua Tang

• Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, PR China

References

• Abdelrahim M, Samudio I, Smith R, Burghardt R, Safe S (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: 28815-28822. doi: 10.1074/jbc.M203828200.
• Black AR, Jensen D, Lin SY, Azizkhan JC (1999) Growth/cell cycle regulation of Sp1 phosphorylation. J Biol Chem 274: 1207-1215. doi: 10.1074/jbc.274.3.1207.
• Chiefari E, Brunetti A, Arturi F, Bidart JM, Russo D, Schlumberger M, Filetti S (2002) Increased expression of AP2 and Sp1 transcription factors in human thyroid tumors: a role in NIS expression regulation? BMC Cancer 2: 35. doi: 10.1186/1471-2407-2-35.
• Cougot D, Neuveut C, Buendia MA (2005) HBV induced carcinogenesis. J Clin Virol 34: S75-S78. doi: doi: 10.1016/S1386-6532(05)80014-9.
• El-Serag HB, Rudolph KL (2007) Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology 132: 2557-2576. doi: doi: 10.1053/j.gastro.2007.04.061.
• Fedi P, Bafico A, Nieto SA, Burgess WH, Miki T, Bottaro DP, Kraus MH, Aaronson SA (1999) Isolation and biochemical characterization of the human Dkk-1 homologue, a novel inhibitor of mammalian Wnt signaling. J Biol Chem 274: 19465-19472. doi: 10.1074/jbc.274.27.19465.
• Forget MA, Turcotte S, Beauseigle D, Godin-Ethier J, Pelletier S, Martin J, Tanguay S, Lapointe R (2007) The Wnt pathway regulator DKK1 is preferentially expressed in hormone-resistant breast tumours and in some common cancer types. Br J Cancer 96: 646-653. doi: 10.1038/sj.bjc.6603579.
• Glinka A, Wu W, Delius H, Monaghan AP, Blumenstock C, Niehrs C (1998) Dickkopf-1 is a member of a new family of secreted proteins and functions in head induction. Nature 391: 357-362. doi: 10.1038/34848.
• González-Sancho JM, Aguilera O, Garcia JM, Pendás-Franco N, Peña C, Cal S, García de Herreros A, Bonilla F, Muñoz A (2005) The Wnt antagonist DICKKOPF-1 gene is a downstream target of beta-catenin/TCF and is downregulated in human colon cancer. Oncogene 24: 1098-1103. doi: 10.1038/sj.onc.1208303.
• Hirose T, Horvitz HR (2013) An Sp1 transcription factor coordinates caspase-dependent and -independent apoptotic pathways. Nature 500: 354-358. doi: 10.1038/nature12329.
• Karlseder J, Rotheneder H, Wintersberger E (1996) Interaction of Sp1 with the growth and cell cycle-regulated transcription factor E2F. Mol Cell Biol 16: 1659-1667. doi: 10.1128/MCB.16.4.1659.
• Keng VW, Tschida BR, Bell JB, Largaespada DA (2011) Modeling hepatitis B virus X-induced hepatocellular carcinoma in mice with the sleeping beauty transposon system. Hepatology 53: 781-790. doi: 10.1002/hep.24091.
• Krupnik VE, Sharp JD, Jiang C, Robison K, Chickering TW, Amaravadi L, Brown DE, Guyot D, Mays G, Leiby K, Chang B, Duong T, Goodearl AD, Gearing DP, Sokol SY, McCarthy SA (1999) Functional and structural diversity of the human Dickkopf gene family. Gene 238: 301-313. doi: 10.1016/S0378-1119(99)00365-0.
• Li L, Davie JR (2010) The role of Sp1 and Sp3 in normal and cancer cell biology. Ann Anat. 192: 275-283. doi: 10.1016/j.aanat.2010.07.010.
• Ling Y, Zhu J, Gao L, Liu Y, Zhu C, Li R (2013) The silence of MUC2 mRNA induced by promoter hypermethylation associated with HBV in hepatocellular carcinoma. BMC Med Genet 14: 14. doi: 10.1186/1471-2350-14-14.
• Liu F, Pore N, Kim M, Voong KR, Dowling M, Maity A, Kao GD (2006) Regulation of histone deacetylase 4 expression by the SP family of transcription factors. Mol Biol Cell 17: 585-597. doi: 10.1091/mbc.E05-08-0775.
• Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2 (-ΔΔC(T)) method. Methods 25: 402-408. doi: 10.1006/meth.2001.1262.
• MacDonald BT, Tamai K, He X (2009) Wnt/β-catenin signaling: components, mechanisms, and diseases. Dev Cell 17: 9-26. doi: 10.1016/j.devcel.2009.06.016.
• Ng SA, Lee C (2011) Hepatitis B virus X gene and hepatocarcinogenesis. J Gastroenterol 46: 974-990. doi: 10.1007/s00535-011-0415-9.
• Patil MA, Chua MS, Pan KH, Lin R, Lih CJ, Cheung ST, Ho C, Li R, Fan ST, Cohen SN, Chen X, So S (2005) An integrated data analysis approach to characterize genes highly expressed in hepatocellular carcinoma. Oncogene 24: 3737-3747. doi: 10.1038/sj.onc.1208479.
• Schutte K, Bornschein J, Malfertheiner P (2009) Hepatocellular carcinoma epidemiological trends and risk factors. Dig Dis 27: 80-92. doi: 10.1159/000218339.
• Tao YM, Liu Z, Liu HL (2013) Dickkopf-1 (DKK1) promotes invasion and metastasis of hepatocellular carcinoma. Dig Liver Dis 45: 251-257. doi: 10.1016/j.dld.2012.10.020.
• Tian YY, Hu Y, Wang ZC, Chen K, Zhang L, Wang LY, Ren M, Huang A, Tang H (2011) Hepatitis B virus regulates Raf1 expression in HepG2.2.15 cells by enhancing its promoter activity. Arch Virol 156: 869-874. doi: 10.1007/s00705-010-0901-z.
• Tung EK, Mak CK, Fatima S, Lo RC, Zhao H, Zhang C, Dai H, Poon RT, Yuen MF, Lai CL, Li JJ, Luk JM, Ng IO (2011) Clinicopathological and prognostic significance of serum and tissue Dickkopf-1 levels in human hepatocellular carcinoma. Liver Int 31: 1494-1504. doi: 10.1111/j.1478-3231.2011.02597.x.
• Wang L, Wei D, Huang S, Peng Z, Le X, Wu TT, Yao J, Ajani J, Xie K (2003) Transcription factor Sp1 expression is a significant predictor of survival in human gastric cancer. Clin Cancer Res 9: 6371-6380.
• Wirths O, Waha A, Weggen S, Schirmacher P, Kühne T, Goodyer CG, Albrecht S, Von Schweinitz D, Pietsch T. (2003) Overexpression of human Dickkopf-1, an antagonist of wingless/WNT signaling, in human hepatoblastomas and Wilms' tumors. Lab Invest 83: 429-434.
• Xu C, Zhou W, Wang Y, Qiao L (2014) Hepatitis B virus-induced hepatocellular carcinoma. Cancer Lett 345: 216-222. doi: 10.1016/j.canlet.2013.08.035.
• Yamashita T, Forgues M, Wang W, Kim JW, Ye Q, Jia H, Budhu A, Zanetti KA, Chen Y, Qin LX, Tang ZY, Wang XW (2008) EpCAM and alpha-fetoprotein expression defines novel prognostic subtypes of hepatocellular carcinoma. Cancer Res 68: 1451-1461. doi: 10.1158/0008-5472.CAN-07-6013.
• Yao M, Yao DF, Bian YZ, Zhang CG, Qiu LW, Wu W, Sai WL, Yang JL, Zhang HJ (2011) Oncofetal antigen glypican-3 as a promising early diagnostic marker for hepatocellular carcinoma. Hepatobiliary Pancreat Dis Int 10: 289-294.
• Yu B, Yang X, Xu Y, Yao G, Shu H, Lin B, Hood L, Wang H, Yang S, Gu J, Fan J, Qin W (2009) Elevated expression of DKK1 is associated with cytoplasmic/nuclear beta-catenin accumulation and poor prognosis in hepatocellular carcinomas. J Hepatol 50: 948-957. doi: 10.1016/j.jhep.2008.11.020.
• Zhou Y, Wang S, Ma JW, Lei Z, Zhu HF, Lei P, Yang ZS, Zhang B, Yao XX, Shi C, Sun LF, Wu XW, Ning Q, Shen GX, Huang B (2010) Hepatitis B virus protein X-induced expression of the CXC chemokine IP-10 is mediated through activation of NF- kappaB and increases migration of leukocytes. J Biol Chem 285: 12159-12168. doi: 10.1074/jbc.M109.067629.

Identifiers

DOI

10.18388/abp.2016_1250