Department of General Surgery, The Ninth Hospital of Xi'an, No 151 South Erhuan Dongduan, Xi'an City, Shaanxi Province 710054, China.
Department of General Surgery, The Ninth Hospital of Xi'an, No 151 South Erhuan Dongduan, Xi'an City, Shaanxi Province 710054, China.
Gene. 2019 Jan 10;681:7-14. doi: 10.1016/j.gene.2018.09.036. Epub 2018 Sep 21.
Proline-rich protein 11 (PRR11) has been shown to play an critical roles in the development of cancer. However, the clinical significance and the biological role of PRR11 in hepatocellular carcinoma (HCC) remains unknown. The present study aimed to investigate the expression pattern, prognostic value and the biological role of PRR11 in HCC. PRR11 expression in 80 HCC surgical specimens was examined, and its clinical significance was analyzed. The role of PRR11 in cell proliferation, colony formation, migration and invasion were also determined. The results showed that PRR11 mRNA was significantly up-regulated in 56.25% (45/80) HCC from that in matched adjacent non-tumor tissues. High PRR11 was correlated with tumor size (P = 0.01) and TNM stage (P = 0.006). Patients with higher PRR11 expression had poor overall survival time (P < 0.001). Furthermore, PRR11 silencing obviously inhibited cell proliferation, colony formation, as well as cell migration and invasion of HCC cell lines in vitro. Mechanistically, knockdown of PRR11 significantly decreased the expression of β-catenin, cyclinD1, c-myc and N-cadherin in HCC cell lines. Additionally, the inhibitory effects of PRR11 silencing on cell migration was significantly enhanced by β-catenin inhibition. PRRl1 mRNA expression was found positively correlated with β-catenin (R = 0.5472, P ˂ 0.0001), c-myc (R = 0.5527, P ˂ 0.0001) and cyclinD1 (R = 0.3948, P = 0.0003) in HCC tissues. Collectively, our data demonstrate that PRR11 plays an oncogenic role in HCC progression, through activating the Wnt/β-catenin signaling pathway, and may represent a valuable prognostic marker and therapeutic target for HCC.
富含脯氨酸蛋白 11（PRR11）已被证明在癌症的发展中发挥关键作用。然而，PRR11 在肝细胞癌（HCC）中的临床意义和生物学作用尚不清楚。本研究旨在探讨 PRR11 在 HCC 中的表达模式、预后价值和生物学作用。检测了 80 例 HCC 手术标本中 PRR11 的表达，并分析了其临床意义。还确定了 PRR11 在细胞增殖、集落形成、迁移和侵袭中的作用。结果表明，56.25%（45/80）的 HCC 中 PRR11 mRNA 显著上调，与配对的相邻非肿瘤组织相比。高 PRR11 与肿瘤大小（P=0.01）和 TNM 分期（P=0.006）相关。PRR11 表达较高的患者总生存时间较差（P<0.001）。此外，PRR11 沉默明显抑制 HCC 细胞系的体外细胞增殖、集落形成以及细胞迁移和侵袭。机制上，PRR11 敲低显著降低了 HCC 细胞系中β-catenin、cyclinD1、c-myc 和 N-cadherin 的表达。此外，PRR11 沉默对细胞迁移的抑制作用通过β-catenin 抑制得到显著增强。PRRl1 mRNA 表达与 HCC 组织中的β-catenin（R=0.5472，P<0.0001）、c-myc（R=0.5527，P<0.0001）和 cyclinD1（R=0.3948，P=0.0003）呈正相关。总之，我们的数据表明，PRR11 通过激活 Wnt/β-catenin 信号通路在 HCC 进展中发挥致癌作用，可能成为 HCC 有价值的预后标志物和治疗靶点。
