Department of Orthopedics, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Shanghai 200233, P.R. China.
Oncol Rep. 2017 Oct;38(4):2116-2122. doi: 10.3892/or.2017.5890. Epub 2017 Aug 8.
Osteosarcoma is the most common malignant bone tumor in adolescents. The function of basic leucine zipper and W2 domains 2 (BZW2) in tumor progression has been reported. However, the role and mechanisms of BZW2 in osteosarcoma remain to be determined. The aim of the present study was to reveal the expression and biological functions of BZW2 in osteosarcoma and to elucidate the proximal mechanisms underlying these functions. The expression of BZW2 in osteosarcoma tissues and cell lines was assessed by qRT-PCR, western blotting and immunohistochemistry. BZW2 overexpression was detected in osteosarcoma cell lines. Clinically, BZW2 expression was higher in osteosarcoma tissues than in corresponding non-tumor tissues and was associated with advanced Enneking stage and tumor recurrence. The knockdown of BZW2 using siRNA inhibited osteosarcoma cell proliferation, colony-forming ability, and the cell cycle at the G2/M phase in vitro. Host signaling pathways affected by BZW2 were detected using a PathScan Intracellular Signaling Antibody Array kit. These data demonstrated that the knockdown of BZW2 suppresses protein phosphorylation in the Akt/mTOR signaling pathway. These observations suggest that BZW2 is upregulated and has a pro-tumor effect in osteosarcoma via activation of the Akt/mTOR signaling pathway and thus is a potential target for gene therapy.
骨肉瘤是青少年中最常见的恶性骨肿瘤。已有报道称，碱性亮氨酸拉链和 W2 结构域 2（BZW2）在肿瘤进展中的功能。然而，BZW2 在骨肉瘤中的作用和机制仍有待确定。本研究旨在揭示 BZW2 在骨肉瘤中的表达和生物学功能，并阐明这些功能的近端机制。通过 qRT-PCR、western blot 和免疫组织化学评估 BZW2 在骨肉瘤组织和细胞系中的表达。在骨肉瘤细胞系中检测到 BZW2 的过表达。临床上，BZW2 的表达在骨肉瘤组织中高于相应的非肿瘤组织，并且与 Enneking 分期较晚和肿瘤复发相关。使用 siRNA 敲低 BZW2 可抑制骨肉瘤细胞在体外的增殖、集落形成能力和 G2/M 期的细胞周期。使用 PathScan 细胞内信号转导抗体阵列试剂盒检测受 BZW2 影响的宿主信号通路。这些数据表明，BZW2 的敲低抑制了 Akt/mTOR 信号通路中蛋白质的磷酸化。这些观察结果表明，BZW2 通过激活 Akt/mTOR 信号通路在上调并在骨肉瘤中发挥促肿瘤作用，因此是基因治疗的潜在靶点。
