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Research Paper

Stable knockdown of Aurora-A by vector-based RNA interference in human esophageal squamous cell carcinoma cell line inhibits tumor cell proliferation, invasion and enhances apoptosis

Xiaoxia Wang, Lijia Dong, Jun Xie, Tong Tong and Qimin Zhan

Esophageal squamous cell carcinoma (ESCC) is one of the most malignant cancers,
and the existing treatment approaches have not been able to effectively manage this
dreaded cancer. Therefore, continuing efforts are ongoing to explore novel targets and
strategies for the management of ESCC. It has been shown that amplification and
overexpression of the Aurora-A occur in several types of human tumors, including
ESCC. Moreover, overexpression of Aurora-A is shown to associate with the grades
of tumor differentiation and metastasis of ESCC. These render Aurora-A an
interesting target for antitumor therapy. Recently, vector-based RNA interference
(RNAi) expression systems have been successfully used to silence gene expression,
but knockdown of Aurora-A by vector-based RNAi as a therapeutic model for ESCC
treatment is not fully established. In this study, we used a DNA vector-based RNAi
approach by expressing short hairpin RNA (shRNA) to knock down Aurora-A.
Western blotting analysis and reverse transcription PCR (RT-PCR) showed that
expressions of Aurora-A were efficiently downregulated at both the protein and
mRNA levels by stable transfection with Aurora-A siRNA expression vector. The
stable suppression of Aurora-A expression inhibited the proliferation and invasion of
EC9706 cells. Furthermore, when Aurora-A was stably downregulated,
cisplatin-induced cytotoxic effects and apoptosis were increased dramatically. These
data indicate that vector-mediated silencing of the Aurora-A gene may provide new
avenues toward the study of the role of Aurora-A overexpression in tumor cells. Make a novel therapeutic approach to treatment of ESCC and other malignant tumors
overexpressing Aurora-A.

Authors

Xiaoxia Wang

State Key Laboratory of Molecular Oncology; Cancer Institute; Chinese Academy of Medical Sciences & Peking Union Medical College; Beijing, China; Departments of Biochemistry and Molecular Biology; Shanxi Medical University; Taiyuan, China

Lijia Dong

State Key Laboratory of Molecular Oncology; Cancer Institute; Chinese Academy of Medical Sciences & Peking Union Medical College; Beijing, China

Jun Xie

Departments of Biochemistry and Molecular Biology; Shanxi Medical University; Taiyuan, China

Tong Tong

State Key Laboratory of Molecular Oncology; Cancer Institute; Chinese Academy of Medical Sciences & Peking Union Medical College; Beijing, China

Qimin Zhan

State Key Laboratory of Molecular Oncology; Cancer Institute; Chinese Academy of Medical Sciences & Peking Union Medical College; Beijing, China