State Key Laboratory of Oral Diseases, West China College of Stomatology, Sichuan University, Chengdu, China.
Mol Cancer. 2010 Jan 28;9:20. doi: 10.1186/1476-4598-9-20.
Oral Cancer Overexpressed 1 (ORAOV1) is a candidate protooncogene locating on 11q13. Recent studies show that ORAOV1 acts as a primary driving force behind 11q13 gene amplification and plays a functional role in the tumorigenesis in a variety of human squamous cell carcinomas (SCCs). According to the results of molecular cytogenetic methods, 11q13 was characterized to be a high-level and recurrent amplification chromosomal site in cervical cancers. Up till now, the role of ORAOV1 in cervical cancer is unknown. The purpose of this study is to elucidate the function of ORAOV1 in cervical cancer cell growth by studying its roles in HeLa cells using small interfering RNA.
Functional analyses revealed that ORAOV1 was involved in the regulation of HeLa cell growth through its effect on cell cycle and apoptosis. Silence of ORAOV1 in HeLa cells downregulated the expression of Cyclin A, Cyclin B1 and Cdc2, and led to a distinct S cell cycle arrest. Moreover, knockdown of ORAOV1 expression activated both extrinsic and intrinsic apoptotic pathways and led to apoptosis in HeLa cells through its effect on the expression of several apoptosis related proteins such as P53, Bcl-2, Caspase-3, Caspase-8, Caspase-9 and cytochrome c. Interestingly, the expression of Cyclin D1, a pivotal gene for cervical cancer tumorigenesis, was also found to be reduced in ORAOV1 silenced HeLa cells.
Our findings indicate that ORAOV1 has an important role in regulating cell growth of cervical cancer HeLa cells through regulating the cell cycle and apoptosis. Thus, it may be a crucial protooncogene and a novel candidate therapeutic target for cervical cancer.
口腔癌过表达 1（ORAOV1）是位于 11q13 的候选原癌基因。最近的研究表明，ORAOV1 是 11q13 基因扩增的主要驱动力，并在多种人类鳞状细胞癌（SCC）的肿瘤发生中发挥功能作用。根据分子细胞遗传学方法的结果，11q13 被认为是宫颈癌中高水平和反复扩增的染色体部位。到目前为止，ORAOV1 在宫颈癌中的作用尚不清楚。本研究旨在通过使用小干扰 RNA 研究其在 HeLa 细胞中的作用，阐明 ORAOV1 在宫颈癌细胞生长中的功能。
功能分析表明，ORAOV1 通过对细胞周期和凋亡的影响参与调节 HeLa 细胞的生长。在 HeLa 细胞中沉默 ORAOV1 下调了细胞周期蛋白 A、B1 和 Cdc2 的表达，并导致明显的 S 期细胞周期停滞。此外，下调 ORAOV1 表达可激活外源性和内源性凋亡途径，并通过影响几种凋亡相关蛋白（如 P53、Bcl-2、Caspase-3、Caspase-8、Caspase-9 和细胞色素 c）的表达导致 HeLa 细胞凋亡。有趣的是，宫颈癌肿瘤发生的关键基因 Cyclin D1 的表达也发现在沉默 ORAOV1 的 HeLa 细胞中减少。
我们的研究结果表明，ORAOV1 通过调节细胞周期和凋亡在调节宫颈癌 HeLa 细胞生长中起重要作用。因此，它可能是一个关键的原癌基因，也是宫颈癌的一个新的候选治疗靶点。
