Department of General Surgery, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai 200240, China.
Department of General Surgery, Fengxian District Central Hospital of Shanghai, Shanghai 201499, China.
Cancer Biomark. 2019;24(1):61-70. doi: 10.3233/CBM-181703.
Nucleoporin NUP153 (NUP153) is well known to be involved in the regulating of nuclear transport. Although NUP153 is associated with several cancers, its role in colorectal cancer (CRC) and the underlying mechanism are still unknown.
The aim of this study was to access the effect of NUP153 on the prognosis of patients with CRC, and cancer cell proliferation.
The expression levels of NUP153 in CRC tissues and matched normal colon tissues were examined by real-time quantitative PCR and immunohistochemistry. Then the association between NUP153 levels with clinical variables as well as survival time was investigated. Moreover, overexpression of NUP153 in HCT116 cells was established to study its influence on cell proliferation in vitro, and a xenograft model was performed to explore this effect in vivo.
We found that NUP153 was highly expressed in adjacent normal tissues than in cancer tissues, and elevated NUP153 expression was negatively associated with pathological grade (P= 0.015), T stage (P= 0.048) and distant metastasis (P= 0.006). Kaplan-Meier analysis revealed that patients with higher NUP153 expression had a longer overall survival (OS) (P= 0.01) and recurrence free disease (RFS) (P= 0.001). Logistic regression analysis further identified NUP153 as an independent prognostic safe factor for OS and recurrence. Moreover, NUP153 overexpression suppressed CRC cells proliferation and inhibited tumor growth in a xenograft model. Its mechanistic investigations showed that NUP153 overexpression inhibited β-catenin transcriptional activity and down-regulated the mRNA expression levels of Wnt downstream proteins-Axin2, cyclinD1, c-myc and lef-1.
NUP153 might be a promising prognostic factor, a potential tumor suppressor and therapeutic target in human CRC through an interaction with the Wnt/β-catenin signaling pathway.
核孔蛋白 NUP153（NUP153）在核转运的调节中起着重要作用。尽管 NUP153 与几种癌症有关，但它在结直肠癌（CRC）中的作用及其潜在机制尚不清楚。
本研究旨在评估 NUP153 对 CRC 患者预后和癌细胞增殖的影响。
通过实时定量 PCR 和免疫组织化学检测 CRC 组织和匹配的正常结肠组织中 NUP153 的表达水平。然后，研究了 NUP153 水平与临床变量和生存时间的相关性。此外，建立了 NUP153 在 HCT116 细胞中的过表达模型，以研究其对细胞增殖的影响，并进行了异种移植模型以探索其在体内的作用。
我们发现 NUP153 在相邻正常组织中的表达高于癌组织，并且升高的 NUP153 表达与病理分级（P=0.015）、T 分期（P=0.048）和远处转移（P=0.006）呈负相关。Kaplan-Meier 分析显示，NUP153 表达较高的患者总生存期（OS）（P=0.01）和无复发生存期（RFS）（P=0.001）更长。Logistic 回归分析进一步确定 NUP153 是 OS 和复发的独立预后安全因素。此外，NUP153 过表达抑制 CRC 细胞增殖，并在异种移植模型中抑制肿瘤生长。其机制研究表明，NUP153 过表达抑制 β-连环蛋白转录活性，并下调 Wnt 下游蛋白-Axin2、cyclinD1、c-myc 和 lef-1 的 mRNA 表达水平。
NUP153 可能通过与 Wnt/β-连环蛋白信号通路相互作用，成为 CRC 中一种有前途的预后因素、潜在的肿瘤抑制因子和治疗靶点。
