Eukaryotic Translation Initiation Factor 3b is both a Promising Prognostic Biomarker and a Potential Therapeutic Target for Patients with Clear Cell Renal Cell Carcinoma.

Eukaryotic Translation Initiation Factor 3b is both a Promising Prognostic Biomarker and a Potential Therapeutic Target for Patients with Clear Cell Renal Cell Carcinoma.
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真核翻译起始因子 3b 既是透明细胞肾细胞癌患者有前景的预后生物标志物,也是潜在的治疗靶点

DOI:
10.7150/jca.19594
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发表时间:
2017
期刊:
影响因子:
3.9
通讯作者:
Xu Z
Xu Z
中科院分区:
医学3区
文献类型:
--
作者:
Zang Y;Zhang X;Yan L;Gu G;Li D;Zhang Y;Fang L;Fu S;Ren J;Xu Z

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真核翻译起始因子(eIFs)是一类新的肿瘤治疗靶点。EIF3b是eIF3 (eIFs的最大核心)的主要支架蛋白。我们试图确定eIF3b在透明细胞肾细胞癌(ccRCC)患者中所起的作用及其作用机制。我们发现肿瘤中高水平的eIF3b表达不仅与侵袭性肿瘤表型相关,而且还与ccRCC患者的预后独立相关。eIF3b的敲低会破坏Akt通路的作用,从而通过破坏细胞周期和触发细胞凋亡来抑制细胞增殖。此外,eIF3b缺失后,通过抑制细胞迁移和侵袭,上皮细胞向间质细胞的转变受到损害。此外,eIF3b敲低显著抑制小鼠皮下异种移植物的生长。综上所述,这些数据表明eIF3b既是一种有前景的预后生物标志物,也是ccRCC患者的潜在治疗靶点。
Eukaryotic translation initiation factors (eIFs) constitute a new class of therapeutic cancer targets. EIF3b is the major scaffold protein of eIF3 (the largest core of eIFs). We sought to define the role played by and the mechanism of action of eIF3b in patients with clear cell renal cell carcinoma (ccRCC). We found that high-level eIF3b expression in tumors was not only associated with an aggressive tumor phenotype, but was also independently prognostic for patients with ccRCC. Knockdown of eIF3b impaired the action of the Akt pathway, thus inhibiting cell proliferation by disrupting the cell cycle and triggering apoptosis. Furthermore, the epithelial-to-mesenchymal transition was impaired after eIF3b depletion, via suppression of cell migration and invasion. Additionally, eIF3b knockdown significantly inhibited the growth of subcutaneous xenografts in mice. Together, these data show that eIF3b is both a promising prognostic biomarker and a potential therapeutic target for patients with ccRCC.
乙型肝炎病毒 X 蛋白通过 ERK 介导的 GSK-3beta 失活来稳定 Cyclin D1 并增加 Cyclin D1 核积累。
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