Oral cancer overexpressed 1 (ORAOV1) regulates cell cycle and apoptosis in cervical cancer HeLa cells.
BACKGROUND
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.


RESULTS
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.


CONCLUSIONS
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.
Jiang
Lu
L
State Key Laboratory of Oral Diseases, West China College of Stomatology, Sichuan University, Chengdu, China.
Zeng
Xin
X
Wang
Zhi
Z
Ji
Ning
N
Zhou
Yu
Y
Liu
Xianting
X
Chen
Qianming
Q
D017209:Apoptosis; D002453:Cell Cycle; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006367:HeLa Cells; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D016196:S Phase; D014410:Tumor Stem Cell Assay; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000473:pathology*; D023041:Xenograft Model Antitumor Assays
C465628:LTO1 protein, human; D009363:Neoplasm Proteins