Abstract:
Identification of novel biomarkers for prediction of disease course and prognosis is needed to reduce morbidity of liver hepatocellular carcinoma (LIHC/HCC) patients. Although dysregulated Periodic tryptophan protein 1 homolog (PWP1/endonuclein) expression has been detected in several tumors, the potential regulatory effect of PWP1 on LIHC remains uncertain. Here we evaluated the expression of PWP1 using multiple online platforms, and demonstrated that PWP1 upregulation was consistently observed in LIHC relative to non-tumor liver tissues and correlated with unfavorable prognosis. Moreover, HCC prognosis was significantly influenced by the methylation status of various CpG sites in the PWP1 gene. Lastly, we provide direct evidence that PWP1 acts as a driver of HCC progression by showing that siRNA-mediated PWP1 silencing significantly suppressed HCC cell proliferation in vitro. These data strongly suggest that PWP1 silencing may be an effective therapeutic strategy to treat LIHC.
摘要:
需要鉴定用于预测病程和预后的新型生物标志物以降低肝细胞癌(LIHC/HCC)患者的发病率。尽管在几种肿瘤中检测到周期性色氨酸蛋白1同源物(PWP1/核酸内切蛋白)表达失调,PWP1对LIHC的潜在调节作用仍不确定。在这里,我们使用多个在线平台评估了PWP1的表达式,并证明在LIHC中相对于非肿瘤肝组织始终观察到PWP1上调,并与不良预后相关。此外,PWP1基因中各种CpG位点的甲基化状态显著影响HCC的预后。最后,通过显示siRNA介导的PWP1沉默在体外显著抑制HCC细胞增殖,我们提供了PWP1作为HCC进展驱动因素的直接证据.这些数据强烈表明PWP1沉默可能是治疗LIHC的有效治疗策略。