核仁与纺锤体相关蛋白1（NUSAP1）通过转化生长因子-β信号通路促进膀胱癌进展。
Nucleolar and Spindle Associated Protein 1 (NUSAP1) Promotes Bladder Cancer Progression Through the TGF-β Signaling Pathway.
作者信息
Gao Shun, Yin Hubin, Tong Hang, Zhan Kai, Yang Guang, Hossain Mohammad Arman, Li Tinghao, Gou Xin, He Weiyang
机构信息
Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China.
Central Laboratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China.
出版信息
Onco Targets Ther. 2020 Jan 28;13:813-825. doi: 10.2147/OTT.S237127. eCollection 2020.
PURPOSE
NUSAP1 has been reported to be involved in the progression of several types of cancer. However, its expression and exact role in bladder cancer (BLCA) remains elusive. The aim of this study was to determine the expression and role of NUSAP1 in BLCA.
METHODS
Tissue microarray, real-time PCR, Western blot and immunohistochemistry assays were carried out to determine NUSAP1 expression in BLCA tissues and cells. The biological roles of NUSAP1 were investigated using CCK-8, EdU labeling, flow cytometry, Transwell, and wound healing assays. Additionally, the effect of NUSAP1 on epithelial-mesenchymal transition (EMT) was investigated by Western blotting and real-time PCR.
RESULTS
We found that NUSAP1 was upregulated in BLCA, and its expression was closely related to the poor prognosis of patients. Subsequently, we transfected 5637 and T24 cell lines with NUSAP1 siRNA and an NUSAP1 overexpression plasmid, respectively. NUSAP1 downregulation in 5637 cells inhibited cell proliferation, migration, and invasiveness and enhanced chemosensitivity to gemcitabine, while NUSAP1 overexpression in T24 cells resulted in the inverse effects. Moreover, NUSAP1 regulated EMT via the TGF-β signaling pathway, and when TGF-beta receptor 1 (TGFBR1) was inhibited with the inhibitor SB525334, the invasion and metastasis ability of BLCA cells was significantly suppressed, as well as p-Smad2/3 and vimentin expression.
CONCLUSION
Our above data demonstrate that NUSAP1 contributes to BLCA progression via the TGF-β signaling pathway.
目的
据报道，NUSAP1参与了多种类型癌症的进展。然而，其在膀胱癌（BLCA）中的表达及确切作用仍不清楚。本研究的目的是确定NUSAP1在BLCA中的表达及作用。
方法
进行组织芯片、实时定量PCR、蛋白质印迹和免疫组织化学分析，以确定NUSAP1在BLCA组织和细胞中的表达。使用CCK-8、EdU标记、流式细胞术、Transwell和伤口愈合实验研究NUSAP1的生物学作用。此外，通过蛋白质印迹和实时定量PCR研究NUSAP1对上皮-间质转化（EMT）的影响。
结果
我们发现NUSAP1在BLCA中上调，其表达与患者的不良预后密切相关。随后，我们分别用NUSAP1 siRNA和NUSAP1过表达质粒转染5637和T24细胞系。5637细胞中NUSAP1的下调抑制了细胞增殖、迁移和侵袭，并增强了对吉西他滨的化学敏感性，而T24细胞中NUSAP1的过表达则产生相反的效果。此外，NUSAP1通过TGF-β信号通路调节EMT，当用抑制剂SB525334抑制TGF-β受体1（TGFBR1）时，BLCA细胞的侵袭和转移能力以及p-Smad2/3和波形蛋白的表达均受到显著抑制。
结论
我们的上述数据表明，NUSAP1通过TGF-β信号通路促进BLCA进展。
Zotero 插件