Abstract
BackgroundUsing gene expression profiling, we previously identified CDC25B to be significantly highly expressed in hepatocellular carcinoma (HCC) compared to non-tumor liver. CDC25B is a cell cycle-activating phosphatase that positively regulates the activity of cyclin-dependent kinases, and is over-expressed in a variety of human malignancies. In this study, we validated the over-expression of CDC25B in HCC, and further investigated its potential as a therapeutic target for the management of HCC.ResultsQuantitative real-time polymerase chain reaction and immunohistochemical staining of patient samples confirmed the significant over-expression of CDC25B in HCC compared to non-tumor liver samples (P < 0.001). Thus, intefering with the expression and activity of CDC25B may be a potential way to intervene with HCC progression. We used RNA interference to study the biological effects of silencing CDC25B expression in HCC cell lines (Hep3B and Hep40), in order to validate its potential as a therapeutic target. Using small oligo siRNAs targeting the coding region of CDC25B, we effectively suppressed CDC25B expression by up to 90%. This was associatetd with significant reductions in cell growth rate, cell migration and invasion through the matrigel membrane, and caused significant cell cycle delay at the G2 phase. Finally, suppression of CDC25B significantly slowed the growth of Hep40 xenografts in nude mice.ConclusionOur data provide evidence that the inhibition of CDC25B expression and activity lead to suppression of tumor cell growth and motility, and may therefore be a feasible approach in the clinical management of HCC.
Highlights
IntroductionWe previously identified CDC25B to be significantly highly expressed in hepatocellular carcinoma (HCC) compared to non-tumor liver
Using gene expression profiling, we previously identified CDC25B to be significantly highly expressed in hepatocellular carcinoma (HCC) compared to non-tumor liver
CDC25B is significantly overexpressed in hepatocellular carcinoma compared to non-tumor liver In an earlier gene expression study of hepatocellular carcinoma, CDC25B was upregulated in tumor compared to non-tumor samples
Summary
We previously identified CDC25B to be significantly highly expressed in hepatocellular carcinoma (HCC) compared to non-tumor liver. Hepatocellular carcinoma (HCC) is the primary adult malignancy of the liver, and is the fifth most frequent cancer in the world [1]. It causes significant mortality, especially in countries where there is a high prevalence of chronic hepatitis B virus and hepatitis C virus infection [2]. CDC25 phosphatases, as activators of the Cdk/cyclins, play critical roles in the regulation of the eukaryotic cell cycle. Because of their overexpression and correlation with poor prognosis in many diverse cancers, CDC25 phosphatases are attractive targets for anticancer drug development. At the same stage of the cell cycle, a large diversity of phosphorylated CDC25B molecules with different properties and functions may be generated via the activity of several independent kinases
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