Ma Ming, Yu Nina
Department of Oncology, Linyi People's Hospital.
Tohoku J Exp Med. 2017 Mar;241(3):239-247. doi: 10.1620/tjem.241.239.
Transducin (β)-like 1 X-linked receptor 1 (TBL1XR1) is a core component of the NCoR/SMRT transcription co-repressor complex, and its role in regulating cancer progression has been reported. Serous epithelial ovarian cancer (EOC) is the most common histological type of EOC. Here we explored the significance of TBL1XR1 expression in predicting outcomes of patients with serous EOC. Real-time quantitative PCR analysis showed that the expression level of TBL1XR1 mRNA was significantly higher in EOC tissues compared with adjacent non-tumorous tissues. The protein levels of TBL1XR1 in EOC tissues were assessed by immunohistochemistry, and the patients were classified into low-expression group (n = 62) and high-expression group (n = 54) according to the immunoreactivity. Prognostic significance of TBL1XR1 was evaluated by univariate and multivariate analyses, showing that over-expression of TBL1XR1 was correlated with poor prognosis. In addition, TBL1XR1 was positively associated with the lymph node metastasis of EOC. Because vascular endothelial growth factor (VEGF)-C is known as a critical mediator of lymph node metastasis, we measured the expression level of VEGF-C mRNA in EOC tissues and thus identified a positive correlation between TBL1XR1 and VEGF-C mRNA levels. Subsequently, using human EOC cell lines, we showed that silencing of TBL1XR1 decreased VEGF-C expression, suggesting that TBL1XR1 may function as an upstream regulator of VEGF-C in EOC. Furthermore, the proliferation and invasion of EOC cells were inhibited by TBL1XR1 silencing. In conclusion, TBL1XR1 overexpression may be an unfavorable prognostic factor for EOC. We also suggest that the TBL1XR1-VEGF-C axis may determine the EOC progression.
转导素（β）样 1 X 连锁受体 1（TBL1XR1）是 NCoR/SMRT 转录共抑制复合物的核心成分，其在调节癌症进展中的作用已有报道。浆液性上皮性卵巢癌（EOC）是卵巢癌最常见的组织学类型。在此，我们探讨了 TBL1XR1 表达在预测浆液性 EOC 患者预后中的意义。实时定量 PCR 分析显示，与相邻非肿瘤组织相比，EOC 组织中 TBL1XR1 mRNA 的表达水平显著更高。通过免疫组织化学评估 EOC 组织中 TBL1XR1 的蛋白水平，并根据免疫反应性将患者分为低表达组（n = 62）和高表达组（n = 54）。通过单因素和多因素分析评估 TBL1XR1 的预后意义，结果表明 TBL1XR1 的过表达与不良预后相关。此外，TBL1XR1 与 EOC 的淋巴结转移呈正相关。由于血管内皮生长因子（VEGF）-C 是淋巴结转移的关键介质，我们测量了 EOC 组织中 VEGF-C mRNA 的表达水平，从而确定了 TBL1XR1 与 VEGF-C mRNA 水平之间的正相关。随后，使用人 EOC 细胞系，我们发现沉默 TBL1XR1 可降低 VEGF-C 的表达，提示 TBL1XR1 可能在 EOC 中作为 VEGF-C 的上游调节因子发挥作用。此外，沉默 TBL1XR1 可抑制 EOC 细胞的增殖和侵袭。总之，TBL1XR1 过表达可能是 EOC 的不良预后因素。我们还认为 TBL1XR1-VEGF-C 轴可能决定 EOC 的进展。
