Yin Jie, Zhang Yi-An, Liu Tao-Tao, Zhu Ji-Min, Shen Xi-Zhong
Department of Gastroenterology, Zhongshan Hospital of Fudan University, Shanghai, China.
PLoS One. 2014 Feb 28;9(2):e89976. doi: 10.1371/journal.pone.0089976. eCollection 2014.
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.
前体mRNA加工因子19（Prp19）可激活前体mRNA剪接体，还可介导DNA损伤反应。在具有功能性p53的细胞中，Prp19过表达会导致细胞凋亡减少，并增加DNA损伤后的细胞存活率。在此我们发现，在p53失活或具有功能性p53的肝癌（HCC）细胞中，由于化疗药物处理下稳定性受损，Prp19表达下调。沉默Prp19表达可增强有无化疗药物处理的HCC细胞的凋亡。此外，高水平的Prp19可能通过调节髓系白血病细胞分化蛋白1的表达来抑制化疗药物诱导的肝癌细胞凋亡。这些结果表明，靶向Prp19可能增强化疗药物对HCC的促凋亡作用。
