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通过小干扰RNA(siRNA)沉默Smad核相互作用蛋白1(SNIP1)可抑制垂体腺瘤细胞的增殖并诱导其凋亡。

Silencing of the Smad nuclear interacting protein 1 (SNIP1) by siRNA inhibits proliferation and induces apoptosis in pituitary adenoma cells.

作者信息

Chen Xianzhen, Xue Fei, Xie Tianhao, Luo Chun

机构信息

Department of Neurosurgery, Changzheng Hospital, Second Military Medical University, No. 415 FengYang Road, Shanghai, 200003, China.

出版信息

Tumour Biol. 2013 Oct;34(5):3071-6. doi: 10.1007/s13277-013-0873-1. Epub 2013 Jul 30.

DOI:10.1007/s13277-013-0873-1
PMID:23897559
Abstract

Smad nuclear interacting protein 1 (SNIP1) gene encodes a protein that contains a conservative C-terminal forkhead-associated domain and functions as a transcriptional coactivator to regulate cell proliferation and cancer progression. This study aimed to investigate the clinical and biological significance of SNIP1 expression in pituitary adenoma. We analyzed SNIP1 expressions in mouse fibroblast L929 cells and mouse pituitary adenoma AtT-20 cells by Western blotting. SNIP1 gene knockdown by small interfering RNA (siRNA) transfection was performed to evaluate SNIP1 function in pituitary adenoma cell lines. As expected, SNIP1 was found to be upregulated in pituitary adenoma cells. The mRNA and protein levels of SNIP1 were inhibited in AtT-20 cells transfected with siRNAs, which led to decreased proliferation, increased apoptosis, and cycle arrest of pituitary adenoma cells. Concomitantly, c-Myc and cyclin D1 protein levels were reduced. These findings may provide novel targets for the treatment of pituitary adenoma.

摘要

Smad核相互作用蛋白1(SNIP1)基因编码一种蛋白质,该蛋白质含有保守的C末端叉头相关结构域,并作为转录共激活因子发挥作用,以调节细胞增殖和癌症进展。本研究旨在探讨SNIP1表达在垂体腺瘤中的临床和生物学意义。我们通过蛋白质印迹法分析了小鼠成纤维细胞L929和小鼠垂体腺瘤AtT-20细胞中SNIP1的表达。通过小干扰RNA(siRNA)转染进行SNIP1基因敲低,以评估SNIP1在垂体腺瘤细胞系中的功能。正如预期的那样,发现SNIP1在垂体腺瘤细胞中上调。用siRNA转染的AtT-20细胞中SNIP1的mRNA和蛋白质水平受到抑制,这导致垂体腺瘤细胞增殖减少、凋亡增加和细胞周期停滞。同时,c-Myc和细胞周期蛋白D1的蛋白质水平降低。这些发现可能为垂体腺瘤的治疗提供新的靶点。

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本文引用的文献

1
Familial isolated pituitary adenomas (FIPA) and the pituitary adenoma predisposition due to mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene.家族性孤立性垂体腺瘤(FIPA)和由于芳香烃受体相互作用蛋白(AIP)基因突变引起的垂体腺瘤易感性。
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侵袭性垂体瘤的治疗。
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Hypoxia-inducible factor-1 alpha, in association with TWIST2 and SNIP1, is a critical prognostic factor in patients with tongue squamous cell carcinoma.缺氧诱导因子-1α 与 TWIST2 和 SNIP1 相关,是舌鳞癌患者的一个关键预后因素。
Oral Oncol. 2011 Feb;47(2):92-7. doi: 10.1016/j.oraloncology.2010.11.014. Epub 2010 Dec 16.
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Magmas, a gene newly identified as overexpressed in human and mouse ACTH-secreting pituitary adenomas, protects pituitary cells from apoptotic stimuli.Magmas,一种新鉴定的在人和鼠 ACTH 分泌性垂体腺瘤中过度表达的基因,可保护垂体细胞免受凋亡刺激。
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Regulation of cyclin D1 gene expression.细胞周期蛋白 D1 基因表达的调控。
Biochem Soc Trans. 2010 Feb;38(Pt 1):217-22. doi: 10.1042/BST0380217.
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Non-functioning pituitary adenomas.无功能垂体腺瘤。
Best Pract Res Clin Endocrinol Metab. 2009 Oct;23(5):625-38. doi: 10.1016/j.beem.2009.05.005.
8
SNIP1: Myc's new helper in transcriptional activation.剪接体1:Myc在转录激活中的新辅助因子。
Mol Cell. 2006 Dec 28;24(6):811-2. doi: 10.1016/j.molcel.2006.12.003.
9
SNIP1 is a candidate modifier of the transcriptional activity of c-Myc on E box-dependent target genes.SNIP1是c-Myc对E盒依赖性靶基因转录活性的候选调节因子。
Mol Cell. 2006 Dec 8;24(5):771-783. doi: 10.1016/j.molcel.2006.11.006.
10
The FHA domain protein SNIP1 is a regulator of the cell cycle and cyclin D1 expression.FHA结构域蛋白SNIP1是细胞周期和细胞周期蛋白D1表达的调节因子。
Oncogene. 2004 Oct 28;23(50):8185-95. doi: 10.1038/sj.onc.1208025.