Epigenetic upregulation of Bak by ZBP-89 inhibits the growth of hepatocellular carcinoma.
In: Biochimica et biophysica acta, Jg. 1833 (2013-12-01), Heft 12, S. 2970-2979
academicJournal
Zugriff:
Zinc-binding protein-89 regulates Bak to facilitate apoptosis in cancer cells. This study examined if zinc-binding protein-89 regulates Bak through an epigenetic mechanism in hepatocellular carcinoma. We first demonstrated that the expression of Bak was reduced but the levels of deoxyribonucleic acid methyltransferase 1 and histone deacetylase 3 were increased in hepatocellular carcinoma cancer tissues compared to the corresponding non-cancer tissues. Moreover, there was a negative correlation between Bak expression and deoxyribonucleic acid methyltransferase 1 levels in hepatocellular carcinoma. Administration of zinc-binding protein-89 downregulated histone deacetylase 3 expression and suppressed the activities of histone deacetylase and deoxyribonucleic acid methyltransferase, which led to maintenance of histone acetylation status, inhibited the binding of methyl-CpG-binding protein 2 to genomic deoxyribonucleic acid and demethylated CpG islands in the Bak promoter in hepatocellular carcinoma cells. Using the xenograft mouse tumor model, we demonstrated that zinc-binding protein-89 or inhibitors of either epigenetic enzymes could stimulate Bak expression, induce apoptosis, and arrest tumor growth and that the maximal effort was achieved when zinc-binding protein-89 and the enzyme inhibitors were used in combination. Conclusively, zinc-binding protein-89 upregulates the expression of Bak by targeting multiple components of the epigenetic pathway in hepatocellular carcinoma.
(© 2013.)
Titel: |
Epigenetic upregulation of Bak by ZBP-89 inhibits the growth of hepatocellular carcinoma.
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Autor/in / Beteiligte Person: | Ye, CG ; Chen, GG ; Ho, RLK ; Merchant, JL ; He, ML ; Lai, PBS |
Zeitschrift: | Biochimica et biophysica acta, Jg. 1833 (2013-12-01), Heft 12, S. 2970-2979 |
Veröffentlichung: | Amsterdam : Elsevier Pub. Co., 2013 |
Medientyp: | academicJournal |
ISSN: | 0006-3002 (print) |
DOI: | 10.1016/j.bbamcr.2013.08.001 |
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