Abstract
Pre-mRNA processing factor 19 (Prp19) activates pre-mRNA spliceosome and also mediates DNA damage response. Prp19 overexpression in cells with functional p53 leads to decreased apoptosis and increases cell survival after DNA damage. Here we showed that in hepatocellular carcinoma (HCC) cells with inactive p53 or functional p53, Prp19 was down-regulated due to the impaired stability under chemotherapeutic drug treatment. Silencing Prp19 expression enhanced apoptosis of HCC cells with or without chemotherapeutic drug treatment. Furthermore high level of Prp19 may inhibit chemotherapeutic drugs induced apoptosis in hepatocellular carcinoma cells through modulating myeloid leukemia cell differentiation 1 expression. These results indicated that targeting Prp19 may potentiate pro-apoptotic effect of chemotherapeutic agents on HCC.
Highlights
Hepatocellular carcinoma (HCC) is the fifth most common cancer and the fourth leading cause of cancer-related mortality worldwide [1]
The results shown that the protein level of Pre-mRNA processing factor 19 (Prp19) was down-regulated by CDDP in a dose- (Fig. 1A) and time-dependent (Fig. 1B) manner, whereas p53 was not activated
Dox, a DNA double-strand break agent, induced down-regulation of Prp19 in Huh7 cells in a dose- and time-dependent manner (Fig. 1E and F), and in SMMC-7721 cells in a dose-dependent manner (Fig. 1G) but not in a time-dependent manner (Fig. 1H). These data indicate that, DNA damage drugs can lead to Prp19 down-regulation in HCC cells in regardless of p53 status
Summary
Hepatocellular carcinoma (HCC) is the fifth most common cancer and the fourth leading cause of cancer-related mortality worldwide [1]. Chemotherapeutic drugs induce the death of apoptotic cell in a mitochondrial pathway by activating BH3-only proteins and neutralizing the anti-apoptotic proteins such as B-cell lymphoma (BCL) 2, BCL-extra large (BCL-xL) and myeloid leukemia cell differentiation 1 (MCL1) [3]. Activities of such antiapoptotic proteins are orchestrated by some tumor suppressors including p53 [4], which plays key roles in apoptosis. Exploring the unknown apoptotic regulator could offer more insight into the chemotherapeutic resistance of HCC
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