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远上游元件结合蛋白1(FUBP1)的上调促进透明细胞肾细胞癌的肿瘤增殖和肿瘤发生。

Upregulation of Far Upstream Element-Binding Protein 1 (FUBP1) Promotes Tumor Proliferation and Tumorigenesis of Clear Cell Renal Cell Carcinoma.

作者信息

Duan Junyao, Bao Xu, Ma Xin, Zhang Yu, Ni Dong, Wang Hanfeng, Zhang Fan, Du Qingshan, Fan Yang, Chen Jianwen, Wu Shengpan, Li Xintao, Gao Yu, Zhang Xu

机构信息

School of Medicine, Nankai University, Tianjin, China.

Department of Urology, State Key Laboratory of Kidney Diseases, Chinese People's Liberation Army General Hospital, PLA Medical School, Beijing, China.

出版信息

PLoS One. 2017 Jan 11;12(1):e0169852. doi: 10.1371/journal.pone.0169852. eCollection 2017.

DOI:10.1371/journal.pone.0169852
PMID:28076379
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5226774/
Abstract

OBJECTIVE

The far upstream element (FUSE)-binding protein 1 (FUBP1) is a transactivator of human c-myc proto-oncogene transcription, with important roles in carcinogenesis. However, the expression pattern and potential biological function of FUBP1 in clear cell renal cell carcinoma (ccRCC) is yet to be established.

METHODS

FUBP1 expression was detected in ccRCC tissues and cell lines by real-time RT-PCR, Western blot analysis, and immunohistochemistry. The correlations of FUBP1 mRNA expression levels with clinicopathological factors were evaluated. The biological function of FUBP1 during tumor cell proliferation was studied by MTS, colony formation, and soft-agar colony formation. The effects of FUBP1 on cell cycle distribution and apoptosis were analyzed by flow cytometry. Western blot analysis was used to identify the potential mechanism of FUBP1 regulating cell cycle and apoptosis.

RESULTS

The levels of FUBP1 mRNA and protein expression were upregulated in human ccRCC tissues compared with adjacent noncancerous tissues. High levels of FUBP1 mRNA expression were associated with higher tumor stage and tumor size. FUBP1 knockdown inhibited cell proliferation and induced cell cycle arrest and apoptosis. Meanwhile, the expression levels of c-myc and p21 mRNA were correlated with that of FUBP1 mRNA.

CONCLUSIONS

FUBP1 acts as a potential oncogene in ccRCC and may be considered as a novel biomarker or an attractive treatment target of ccRCC.

摘要

目的

远上游元件(FUSE)结合蛋白1(FUBP1)是人类c-myc原癌基因转录的反式激活因子,在肿瘤发生中起重要作用。然而,FUBP1在透明细胞肾细胞癌(ccRCC)中的表达模式及潜在生物学功能尚未明确。

方法

采用实时逆转录聚合酶链反应(RT-PCR)、蛋白质免疫印迹分析及免疫组织化学法检测ccRCC组织及细胞系中FUBP1的表达。评估FUBP1 mRNA表达水平与临床病理因素的相关性。通过MTS法、集落形成实验及软琼脂集落形成实验研究FUBP1在肿瘤细胞增殖过程中的生物学功能。采用流式细胞术分析FUBP1对细胞周期分布及凋亡的影响。运用蛋白质免疫印迹分析确定FUBP1调控细胞周期及凋亡的潜在机制。

结果

与癌旁非肿瘤组织相比,人类ccRCC组织中FUBP1 mRNA及蛋白表达水平上调。FUBP1 mRNA高表达与更高的肿瘤分期及肿瘤大小相关。FUBP1基因敲低抑制细胞增殖,诱导细胞周期阻滞及凋亡。同时,c-myc及p21 mRNA表达水平与FUBP1 mRNA表达水平相关。

结论

FUBP1在ccRCC中作为一种潜在癌基因发挥作用,可能被视为ccRCC的一种新型生物标志物或有吸引力的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d9ec/5226774/cb4a2c69a809/pone.0169852.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d9ec/5226774/814f6a368545/pone.0169852.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d9ec/5226774/75e470959178/pone.0169852.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d9ec/5226774/49ed98b57fe2/pone.0169852.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d9ec/5226774/6118dd47d5a9/pone.0169852.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d9ec/5226774/cb4a2c69a809/pone.0169852.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d9ec/5226774/814f6a368545/pone.0169852.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d9ec/5226774/75e470959178/pone.0169852.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d9ec/5226774/49ed98b57fe2/pone.0169852.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d9ec/5226774/6118dd47d5a9/pone.0169852.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d9ec/5226774/cb4a2c69a809/pone.0169852.g005.jpg

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