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Title: The Roles of Histone Deacetylases 1 and 2 in Hepatocellular carcinoma
Keywords: Histone deacetylase, hepatocellular carcinoma, liver, cancer, survival, tumor
Issue Date: 26-Jul-2011
Source: LEUNG HO WING, CAROL (2011-07-26). The Roles of Histone Deacetylases 1 and 2 in Hepatocellular carcinoma. ScholarBank@NUS Repository.
Abstract: Liver cancer is a disease that is more prevalent in Asia than the rest of the world. Of the various types of liver cancers, hepatocellular carcinoma (HCC) is the most common. The development of HCC is a multi-step process. During this process, the aberrant expression and activities of various genes contribute to the survival and proliferation of tumor cells. One family of proteins that is known to suppress the expression of tumor suppressor genes is histone deacetylase (HDAC). The inhibition of HDACs, by means of various classes of drugs collectively known as HDAC inhibitors, is currently being examined as a strategy to kill tumor cells. In this study, we identified two members of the HDAC family to be highly expressed in human HCC tissue. Both HDAC1 and HDAC2 were upregulated in the HCC tumors compared to the matched non-tumor controls, and HDAC1 expression was found to be correlated with poor prognosis in the patients. When both HDAC1 and 2 were silenced in HCC cell lines, there was reduced colony formation, reduced proliferation, and increased apoptosis in the cells. These effects are attributed to the enzymatic activities of these 2 proteins, which have a compensatory effect on each other?s expressions and activities. In addition, we also examined the change in gene expression profiles in HCC cells when HDAC1 and 2 were silenced individually and together, in comparison to the use of HDAC inhibitor PXD101. Together, these results established the critical roles of HDAC1 and 2 in the survival and proliferation of HCC cells. We have also elicited their mechanism of actions by demonstrating the importance of their enzymatic activity as well as the compensatory effects on each other. Understanding these 2 members of the HDAC family would have significant impact on the design and use of HDAC inhibitors in the treatment of HCC.
Appears in Collections:Ph.D Theses (Open)

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