Silencing Id-1 inhibits lymphangiogenesis through down-regulation of VEGF-C in oral squamous cell carcinoma

Silencing Id-1 inhibits lymphangiogenesis through down-regulation of VEGF-C in oral squamous cell carcinoma
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DOI:
10.1016/j.oraloncology.2010.10.012
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发表时间:
2011-01-01
期刊:
影响因子:
4.8
通讯作者:
Liu, Shaohua
Liu, Shaohua
中科院分区:
医学2区
文献类型:
--
作者:
Dong, Zuoqing;Wei, Fengcai;Liu, Shaohua

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我们的前期研究表明分化抑制因子Id-1(inhibitor of differentiation/DNA binding)的过度表达与口腔鳞状细胞癌(oral squamous cell carcinoma,OSCC)的淋巴结转移有关。本研究进一步揭示了Id-1与血管内皮生长因子-C(VEGF-C)和肿瘤周围淋巴管密度(PLVD)的关系,以及沉默Id-1对抑制口腔鳞癌淋巴管生成的作用。我们发现Id-1与VEGF-C(r = 0.569,p < 0.001)和PLVD(r = 0.240,p < 0.001)相关。慢病毒介导的RNA干扰在口腔鳞癌细胞系Tca 8113中靶向Id-1,导致VEGF-C下调(p = 0.003,0.007)。此外,当通过将Id-1-siRNA-慢病毒注射到裸鼠的移植肿瘤中来抑制Id-1时,VEGF-C下调(p = 0.018)并且PLVD降低(p = 0.001)。我们的研究结果表明,Id-1与淋巴管生成在口腔鳞癌。沉默Id-1可通过下调VEGF-C表达抑制淋巴管生成,有望成为治疗口腔鳞癌淋巴道转移的有效方法。(C)2010爱思唯尔有限公司版权所有。
Our previous study demonstrated that overexpression of Id-1 (inhibitor of differentiation/DNA binding) was associated with lymphatic metastasis in human oral squamous cell carcinoma (OSCC). In this study, we further unveiled the association of Id-1 with vascular endothelial growth factor-C (VEGF-C) and peritumoral lymphatic vessel density (PLVD), and the effect of silencing Id-1 on inhibiting lymphangiogenesis in OSCC. We found that Id-1 was associated with VEGF-C (r = 0.569, p < 0.001) and PLVD (r = 0.240, p < 0.001) in OSCC. Lentivirus-mediated RNA interference targeting Id-1 in an OSCC cell line Tca8113 resulted in down-regulation of VEGF-C (p = 0.003, 0.007). Moreover, when Id-1 was suppressed by injecting Id-1-siRNA-lentivirus into the transplanted tumors in nude mice, VEGF-C was down-regulated (p = 0.018) and the PLVD decreased (p = 0.001). Our results suggest that Id-1 was correlated with lymphangiogenesis in OSCC. Silencing Id-1 could inhibit lymphangiogenesis through down-regulation of VEGF-C and it might be a promising treatment modality for the lymphatic metastasis of OSCC. (C) 2010 Elsevier Ltd. All rights reserved.