Department of Laparoscopy, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, P.R. China.
The First Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, P.R. China.
Oncol Rep. 2017 Aug;38(2):1083-1090. doi: 10.3892/or.2017.5785. Epub 2017 Jul 3.
Paired-related homeobox 1 (PRRX1) has been identified as a novel molecule associated with induction of epithelial-mesenchymal transition (EMT), acquisition of cancer stem cell like properties and poor prognosis in tumors. However, the function of PRRX1 in hepatocellular carcinoma has not been elucidated. In the present study, we observed that PRRX1 expression levels were downregulated and positively correlated with the downregulated expression of p53 in hepatocellular carcinoma specimens. Decreased expression of PRRX1 and/or p53 by siRNA induced both the migration and the invasion features of HCC cells in vitro. Furthermore, the loss of PRRX1 inhibits hepatocellular carcinoma (HCC) cell apoptosis, an anti-apoptotic expression profile was upregulated accompanied by downregulated expression of p53. HCC patients with low-expression of both PRRX1 and p53 had a significantly shorter overall and disease-free survival. These findings demonstrate that PRRX1 plays an important role in metastasis and apoptosis of HCC cells through the p53-dependent signaling pathway and is expected to become a novel biomarker associated with patient prognosis and survival.
配对相关同源盒 1（PRRX1）已被鉴定为一种与上皮-间充质转化（EMT）的诱导、获得癌症干细胞样特性以及肿瘤预后不良相关的新型分子。然而，PRRX1 在肝细胞癌中的功能尚未阐明。在本研究中，我们观察到 PRRX1 的表达水平下调，并且与肝细胞癌标本中 p53 的下调表达呈正相关。siRNA 下调 PRRX1 和/或 p53 的表达均可诱导 HCC 细胞在体外的迁移和侵袭特征。此外，PRRX1 的缺失抑制了肝细胞癌（HCC）细胞的凋亡，同时伴随着 p53 的下调而上调抗凋亡表达谱。PRRX1 和 p53 均低表达的 HCC 患者的总生存期和无病生存期明显缩短。这些发现表明，PRRX1 通过 p53 依赖性信号通路在 HCC 细胞的转移和凋亡中发挥重要作用，有望成为与患者预后和生存相关的新型生物标志物。
