Nucleolar and Spindle Associated Protein 1 (NUSAP1) Promotes Bladder Cancer Progression Through the TGF-β Signaling Pathway
Nucleolar and Spindle Associated Protein 1 (NUSAP1) Promotes Bladder Cancer Progression Through the TGF-β Signaling Pathway
复制标题
核仁和纺锤体相关蛋白 1 (NUSAP1) 通过 TGF-β 信号通路促进膀胱癌进展
DOI：
10.2147/ott.s237127
复制
发表时间：
2020-01-01
影响因子：
4
通讯作者：
He, Weiyang
中科院分区：
文献类型：
--
作者：
Gao, Shun;Yin, Hubin;He, Weiyang
NUSAP1已被报道参与多种类型癌症的进展。然而，其在膀胱癌（BLCA）中的表达和确切作用尚不清楚。本研究的目的是确定NUSAP1在BLCA中的表达及其作用。方法采用组织芯片、实时PCR、Western blot和免疫组化检测NUSAP1在BLCA组织和细胞中的表达。通过CCK-8、EdU标记、流式细胞术、Transwell和伤口愈合试验研究NUSAP1的生物学作用。此外，采用Western blot和real-time PCR检测NUSAP1对上皮-间质转化（epithelial-mesenchymal transition， EMT）的影响。结果我们发现NUSAP1在BLCA中表达上调，其表达与患者预后不良密切相关。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的下调抑制了细胞的增殖、迁移和侵袭性，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作用。此外，NUSAP1通过TGF-β信号通路调控EMT，当使用抑制剂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vimentin的表达均明显受到抑制。结论NUSAP1通过TGF-β信号通路参与BLCA的进展。
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.