NUP153 overexpression suppresses the proliferation of colorectal cancer by negatively regulating Wnt/β-catenin signaling pathway and predicts good prognosis.
Yibin Wu, Guojiu Fang, Xin Wang, Huipeng Wang, Wenjie Chen, Liang Li, Tao Ye, Lifeng Gong, Chongwei Ke, Yuankun Cai
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引用次数: 10
Abstract
Background: 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.
Objective: The aim of this study was to access the effect of NUP153 on the prognosis of patients with CRC, and cancer cell proliferation.
Methods: 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.
Results: 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.
Conclusions: 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.
期刊介绍：
Concentrating on molecular biomarkers in cancer research, Cancer Biomarkers publishes original research findings (and reviews solicited by the editor) on the subject of the identification of markers associated with the disease processes whether or not they are an integral part of the pathological lesion.
The disease markers may include, but are not limited to, genomic, epigenomic, proteomics, cellular and morphologic, and genetic factors predisposing to the disease or indicating the occurrence of the disease. Manuscripts on these factors or biomarkers, either in altered forms, abnormal concentrations or with abnormal tissue distribution leading to disease causation will be accepted.
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