Department of Orthopaedic Surgery, Kyushu University, Fukuoka, Japan.
Br J Cancer. 2013 Mar 5;108(4):836-47. doi: 10.1038/bjc.2012.579.
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.
发生远处转移和局部复发的骨肉瘤(OS)患者预后仍较差。Y 盒结合蛋白-1(YB-1)是一种多功能蛋白,可作为转录和翻译的调节剂,YB-1 蛋白在 OS 中高表达,但 YB-1 在 OS 中的作用尚不清楚。
采用特异性小干扰 RNA 抑制 OS 细胞中 YB-1 的表达(si-YB-1)。分析 si-YB-1 对 OS 细胞体内外增殖和细胞周期转变的影响。采用免疫组织化学方法研究 YB-1 的核表达与临床预后的关系。
体内和体外实验均显示,si-YB-1 抑制 OS 细胞的增殖。si-YB-1 还降低了细胞周期蛋白 D1 和细胞周期蛋白 A 的表达。此外,si-YB-1 诱导 OS 细胞系中 G1/S 期阻滞,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 患者总体生存率显著相关。
YB-1 可在体外和体内调节人 OS 细胞的细胞周期进展和肿瘤生长。YB-1 的核表达与 OS 的预后密切相关,因此,YB-1 同时可能是 OS 的有效分子靶点和预后生物标志物。