Y-box binding protein-1 regulates cell proliferation and is associated with clinical outcomes of osteosarcoma.

Y-box binding protein-1 regulates cell proliferation and is associated with clinical outcomes of osteosarcoma.
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DOI:
10.1038/bjc.2012.579
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发表时间:
2013-03-05
影响因子:
8.8
通讯作者:
Iwamoto, Y.
Iwamoto, Y.
中科院分区:
医学1区
文献类型:
--
作者:
Fujiwara-Okada, Y.;Matsumoto, Y.;Fukushi, J.;Setsu, N.;Matsuura, S.;Kamura, S.;Fujiwara, T.;Iida, K.;Hatano, M.;Nabeshima, A.;Yamada, H.;Ono, M.;Oda, Y.;Iwamoto, Y.

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伴有远处转移和局部复发的骨肉瘤(OS)的预后仍然较差。 Y-box结合蛋白-1(YB-1)是一种多功能蛋白,可作为转录和翻译的调节因子,在OS中观察到YB-1蛋白的高表达,然而,YB-1在OS中的作用仍不清楚。 OS 细胞中 Y-box 结合蛋白-1 的表达受到 YB-1 特异性小干扰 RNA (si-YB-1) 的抑制。体外和体内分析了si-YB-1对OS细胞增殖和细胞周期转变的影响。还通过免疫组织化学研究了 YB-1 核表达与临床预后的关联。 si-YB-1在体内和体外均抑制OS细胞的增殖。 si-YB-1 也降低了 cyclin D1 和 cyclin A 的表达。此外,si-YB-1 在 OS 细胞系中诱导 G1/S 期阻滞,同时细胞周期蛋白 D1 和细胞周期蛋白 A 减少。还观察到 YB-1 在 OS 细胞系中的直接结合。最后,YB-1 的核表达与 OS 患者较差的总生存率显着相关。 Y-box 结合蛋白-1 将在体外和体内调节人 OS 细胞中 G1/S 的细胞周期进程和肿瘤生长。 YB-1的核表达与OS的预后密切相关,因此,YB-1同时可以成为OS的有效分子靶点和预后生物标志物。
Prognosis of osteosarcoma (OS) with distant metastasis and local recurrence is still poor. Y-box binding protein-1 (YB-1) is a multifunctional protein that can act as a regulator of transcription and translation and its high expression of YB-1 protein was observed in OS, however, the role of YB-1 in OS remains unclear. Y-box binding protein-1 expression in OS cells was inhibited by specific small interfering RNAs to YB-1 (si-YB-1). The effects of si-YB-1 in cell proliferation and cell cycle transition in OS cells were analysed in vitro and in vivo. The association of nuclear expression of YB-1 and clinical prognosis was also investigated by immunohistochemistry. Proliferation of OS cell was suppressed by si-YB-1 in vivo and in vitro. The expression of cyclin D1 and cyclin A were also decreased by si-YB-1. In addition, si-YB-1 induced G1/S arrest with decreased cyclin D1 and cyclin A in OS cell lines. Direct binding of YB-1 in OS cell lines was also observed. Finally, the nuclear expression of YB-1 was significantly related to the poorer overall survival in OS patients. Y-box binding protein-1 would regulate cell cycle progression at G1/S and tumour growth in human OS cells in vitro and in vivo. Nuclear expression of YB-1 was closely associated with the prognosis of OS, thus, YB-1 simultaneously could be a potent molecular target and prognostic biomarker for OS.
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