Oral cancer overexpressed 1 (ORAOV1): A regulator for the cell growth and tumor angiogenesis in oral squamous cell carcinoma
Oral cancer overexpressed 1 (ORAOV1): A regulator for the cell growth and tumor angiogenesis in oral squamous cell carcinoma
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口腔癌过表达 1 (ORAOV1)：口腔鳞状细胞癌中细胞生长和肿瘤血管生成的调节因子
DOI：
10.1002/ijc.23734
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发表时间：
2008-10-15
影响因子：
6.4
通讯作者：
Chen, Qianming
中科院分区：
文献类型：
--
作者：
Jiang, Lu;Zeng, Xin;Chen, Qianming
口腔癌过表达1 （ORAOV1）是一个位于染色体11q13带的新基因。最近的研究表明，它在口腔鳞状细胞癌（OSCC）中作为候选癌基因的作用及其对OSCC患者的预后价值。到目前为止，ORAOV1在OSCC中的具体功能仍未明确。在这项研究中，我们通过下调ORAOV1的表达来研究其在OSCC肿瘤发生中的作用。小干扰RNA （Small interfering RNA, siRNA）已被应用于抑制ORAOV1在OSCC细胞中的表达。我们发现ORAOV1减少的OSCC细胞在体外表现出细胞生长迟缓，在体内表现出肿瘤生长和肿瘤血管生成的抑制作用。进一步的分析表明，细胞生长迟缓与凋亡增加有关，包括caspase 3依赖性途径的激活和细胞周期阻滞在S期，细胞周期蛋白a、细胞周期蛋白B1和cdc2的下调。体内抑制肿瘤生长可能与抑制细胞生长和抑制肿瘤血管生成之间的协同作用有关。后者最有可能是因为VEGF受到抑制。综上所述，我们证明ORAOV1在OSCC的生长和血管生成中起关键作用。因此，ORAOV1可能是一个新的靶点，可以探索制定OSCC治疗策略。©2008 Wiley‐Liss, Inc。
Oral Cancer Overexpressed 1 (ORAOV1) is a novel gene locating at chromosome band 11q13. Recent studies have suggested its role as a candidate oncogene in oral squamous cell carcinoma (OSCC) and its prognostic value for patients with OSCC. Till now, the detailed function of ORAOV1 in OSCC has remained undefined. In this study, we have investigated the role of ORAOV1 in OSCC tumorigenesis by down‐regulating its expression. Small interfering RNA (siRNA) has been applied to inhibit the expression of ORAOV1 in OSCC cells. We found that the OSCC cells with reduced ORAOV1 showed retarded cell growth in vitro and displayed inhibition in both tumor growth and tumor angiogenesis in vivo. Further analyses reveal that the retarded cell growth is associated with an increase in apoptosis involving the activation of caspase 3‐dependent pathway and a cell cycle arrest at the S‐phase with a downregulation of cyclin A, cyclin B1 and cdc2. The suppressed tumor growth in vivo may be attributed to synergistic effect between inhibition in cell growth and suppression of tumor angiogenesis. The latter is most likely because of a suppression of VEGF. Taken together, we demonstrate that ORAOV1 plays pivotal roles in the growth and angiogenesis of OSCC. Thus, ORAOV1 may be a novel target that could be explored to develop therapeutic strategy in OSCC management. © 2008 Wiley‐Liss, Inc.