Project B2

Functional Consequences of Altered microRNA Expression Induced by Histone Deacetylation in Hepatocellular Carcinoma

Principal Investigators: Dr. rer nat. Britta Skawran, Prof. Dr. Brigitte Schlegelberger


Short Summary

Alterations in histone acetylation is a common hallmark in human tumor cells and this process strongly alters the transcription of many genes involved in the control of proliferation, cell survival, differentiation and genetic stability. We have shown that histone deacetylases (HDAC1-4) are consistently upregulated in poorly differentiated HCC and that the expression of microRNAs is strongly influenced by histone modifications. We therefore aim to understand the functional effects of altered microRNA expression induced by histone deacetylation in the development and progression of hepatocellular carcinoma (HCC).


List of relevant publications

  1. Bertram C, von Neuhoff N, Skawran B, Steinemann D, Schlegelberger B, Hass R (2008) The differentiation/retrodifferentiation program of human U937 leukemia cells is accompanied by changes of VCP/p97. BMC Cell Biol 9:12
  2. Skawran B, Steinemann D, Weigmann A, Flemming P, Becker T, Flik J, Kreipe H, Schlegelberger B, Wilkens L (2008) Gene expression profiling in hepatocellular carcinoma: Upregulation of genes in amplified chromosome regions. Mod Pathol 21:505-16.
  3. Hertz S, Rothämel T, Skawran B, Giere C, Steinemann D, Flemming P, Becker T, Flik J, Wiese B, Soudah B, Kreipe H, Schlegelberger B, Wilkens L (2008) Losses of chromosome arms 4q, 8p, 13q and gain of 8q are correlated with increasing chromosomal instability in hepatocellular carcinoma. Pathobiology 75:312-22.
  4. Skawran B, Steinemann D, Becker T, Buurman R, Flik J, Wiese B, Flemming P, Kreipe H, Schlegelberger B, Wilkens L (2008) Loss of 13q is associated with genes involved in cell cycle and proliferation in dedifferentiated hepatocellular carcinoma. Mod Pathol 21:1479-89.
  5. Schaetzlein S, Kodandaramireddy NR, Ju Z, Lechel A, Stepczynska A, Lilli DR, Clark AB, Rudolph C, Wei K, Schlegelberger B, Schirmacher P, Kunkel TA, Greenberg RA, Edelmann W, Rudolph KL (2007) Exonuclease-1 deletion impairs DNA damage signaling and prolongs lifespan of telomere-dysfunctional mice. Cell 130:863-77.
  6. Ripperger T, von Neuhoff N, Kamphues K, Emura M, Lehmann U, Tauscher M, Schraders M, Groenen P, Skawran B, Rudolph C, Callet-Bauchu E, van Krieken JH, Schlegelberger B, Steinemann D (2007) Promoter methylation of PARG1, a novel candidate tumor suppressor gene in mantle-cell lymphomas. Haematologica 92:460-68
  7. Steinemann D*, Skawran B*, Becker T, Tauscher M, Weigmann A, Wingen L, Tauscher S, Hinrichsen T, Hertz S, Flemming P, Flik J, Wiese B, Kreipe H, Lichter P, Schlegelberger B, Wilkens L (2006) Assessment of differentiation and progression of hepatic tumors using array- based comparative genomic hybridization. Clin Gastroenterol Hepatol 4:1283-91. (*contributed equally)
  8. Staal FJT, Cario G, Cazzaniga G, Haferlach T, Heuser M, Hofmann W-K, Mills K, Schrappe M, Stanulla M, Wingen LU, van Dongen JJM and Schlegelberger B (2006) Consensus guidelines for microarray gene expression analyses in leukemia from three European leukemia networks. Leukemia 20:1385-92.
  9. Braig M, Lee S, Loddenkemper C, Rudolph C, Peters AH, Schlegelberger B, Stein H, Dorken B, Jenuwein T, Schmitt CA (2005) Oncogene-induced senescence as an initial barrier in lymphoma development. Nature 436:660-65.
  10. Kustikova O, Fehse B, Modlich U, Yang M, Dullmann J, Kamino K, von Neuhoff N, Schlegelberger B, Li Z, Baum C (2005) Clonal dominance of hematopoietic stem cells triggered by retroviral gene marking. Science 308:1171-43.
  11. Wilkens L, Flemming P, Gebel M, Bleck J, Terkamp C, Wingen LU, Kreipe H, Schlegelberger B (2004) Induction of aneuploidy by increasing chromosomal instability during dedifferentiation of hepatocellular carcinoma. Proc Natl Acad Sci USA 101:1309-14.
  12. Plentz RR, Schlegelberger B, Flemming P, Gebel P, Kreipe H, Manns MP, Rudolph KL, Wilkens L (2005) Telomere shortening correlates with increasing aneuploidy of chromosome 8 on a cellular level in primary human hepatocellular carcinoma. Hepatology 42:522-26.
  13. Cario G, Stanulla M, Fine BM, Teuffel O, von Neuhoff N, Schrauder A, Flohr T, Schäfer BW, Bartram CR, Welte K, Schlegelberger B, Schrappe M (2005) Distinct gene expression profiles determine molecular treatment response in childhood acute lymphoblastic leukemia. Blood 105:821-26.
  14. Skawran B, Schubert S, Dechend F, Vervoorts J, Nayernia K, Lüscher B, Schmidtke J (2005) Characterization of a human TSPY promoter. Mol Cell Biochem 276:159-67.



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