Silencing of Aurora kinase A by RNA interference inhibits tumor growth in human osteosarcoma cells by inducing apoptosis and G2/M cell cycle arrest

Jiang,Zhenhuan; Jiang,Jiannong; Yang,Huilin; Ge,Zhijun; Wang,Qiang; Zhang,Leiyan; Wu,Chenguang; Wang,Jinzhi

doi:10.3892/or.2014.2986

2014-March Volume 31 Issue 3

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2014-March Volume 31 Issue 3

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Article

Silencing of Aurora kinase A by RNA interference inhibits tumor growth in human osteosarcoma cells by inducing apoptosis and G2/M cell cycle arrest

Authors:
- Zhenhuan Jiang
- Jiannong Jiang
- Huilin Yang
- Zhijun Ge
- Qiang Wang
- Leiyan Zhang
- Chenguang Wu
- Jinzhi Wang
View Affiliations / Copyright

Affiliations: Department of Orthopaedics, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China, Department of Orthopaedics, People's Hospital of Yixing City, Yixing, Jiangsu 214200, P.R. China, Department of Anesthesiology, People's Hospital of Yixing City, Yixing, Jiangsu 214200, P.R. China, Department of Cell Biology, School of Medicine, Soochow University, Suzhou, Jiangsu 215123, P.R. China
Pages: 1249-1254
|
Published online on: January 20, 2014

https://doi.org/10.3892/or.2014.2986
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Abstract

The overexpression of Aurora kinase A (AURKA), a member of serine/threonine kinase family, has been observed in various types of human cancers. However, the role of AURKA in osteosarcoma (OS), the most common type of primary malignancy arising from bone, has not been clarified. We used AURKA-specific lentivirus-delivered short hairpin RNA (shRNA) to significantly and sustainably silence the endogenous AURKA expression in human OS cells SAOS-2 and U2OS. We found that AURKA downregulation in OS cells prominently decreased colony formation ability in vitro and tumorigenesis ability in vivo. We further evaluated the effect of AURKA silence on cell viability by MTT assay, cell apoptosis and cell cycle by ﬂow cytometer detection. The results showed that AURKA silence inhibited cell viability by inducing cell apoptosis and G2/M cell cycle arrest in OS cells. Taken together, our findings indicate that AURKA plays a crucial role on OS growth by inhibiting cell apoptosis and propelling cell cycle. Inhibition of AURKA by lentivirus-delivered specific shRNA showed the therapeutic potential in treatment of osteosarcoma.

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1	Dorfman HD and Czerniak B: Bone cancers. Cancer. 75:203–210. 1995. View Article : Google Scholar : PubMed/NCBI
2	Bielack SS, Kempf-Bielack B, Delling G, et al: Prognostic factors in high-grade osteosarcoma of the extremities or trunk: an analysis of 1,702 patients treated on neoadjuvant cooperative osteosarcoma study group protocols. J Clin Oncol. 20:776–790. 2002. View Article : Google Scholar
3	Culver KW, Anderson WF and Blaese RM: Lymphocyte gene therapy. Hum Gene Ther. 2:107–109. 1991. View Article : Google Scholar
4	Abdelrahim M, Safe S, Baker C and Abudayyeh A: RNAi and cancer: implications and applications. J RNAi Gene Silencing. 2:136–145. 2006.PubMed/NCBI
5	Rubinson DA, Dillon CP, Kwiatkowski AV, et al: A lentivirus-based system to functionally silence genes in primary mammalian cells, stem cells and transgenic mice by RNA interference. Nat Genet. 33:401–406. 2003. View Article : Google Scholar : PubMed/NCBI
6	Manilla P, Rebello T, Afable C, et al: Regulatory considerations for novel gene therapy products: a review of the process leading to the first clinical lentiviral vector. Hum Gene Ther. 16:17–25. 2005. View Article : Google Scholar : PubMed/NCBI
7	Dutertre S, Descamps S and Prigent C: On the role of aurora-A in centrosome function. Oncogene. 21:6175–6183. 2002. View Article : Google Scholar : PubMed/NCBI
8	Tong T, Zhong Y, Kong J, et al: Overexpression of Aurora-A contributes to malignant development of human esophageal squamous cell carcinoma. Clin Cancer Res. 10:7304–7310. 2004. View Article : Google Scholar : PubMed/NCBI
9	Tanaka E, Hashimoto Y, Ito T, et al: The clinical significance of Aurora-A/STK15/BTAK expression in human esophageal squamous cell carcinoma. Clin Cancer Res. 11:1827–1834. 2005. View Article : Google Scholar : PubMed/NCBI
10	Li D, Zhu J, Firozi PF, et al: Overexpression of oncogenic STK15/BTAK/Aurora A kinase in human pancreatic cancer. Clin Cancer Res. 9:991–997. 2003.PubMed/NCBI
11	Gritsko TM, Coppola D, Paciga JE, et al: Activation and overexpression of centrosome kinase BTAK/Aurora-A in human ovarian cancer. Clin Cancer Res. 9:1420–1426. 2003.PubMed/NCBI
12	Miyoshi Y, Iwao K, Egawa C and Noguchi S: Association of centrosomal kinase STK15/BTAK mRNA expression with chromosomal instability in human breast cancers. Int J Cancer. 92:370–373. 2001. View Article : Google Scholar : PubMed/NCBI
13	Sen S, Zhou H, Zhang RD, et al: Amplification/overexpression of a mitotic kinase gene in human bladder cancer. J Natl Cancer Inst. 94:1320–1329. 2002. View Article : Google Scholar : PubMed/NCBI
14	Bacci G, Ferrari S, Mercuri M, et al: Neoadjuvant chemotherapy for osteosarcoma of the extremities in patients aged 41–60 years: outcome in 34 cases treated with adriamycin, cisplatinum and ifosfamide between 1984 and 1999. Acta Orthop. 78:377–384. 2007.
15	Murdoch D and Sager J: Will targeted therapy hold its promise? an evidence-based review. Curr Opin Oncol. 20:104–111. 2008. View Article : Google Scholar : PubMed/NCBI
16	Li CX, Parker A, Menocal E, Xiang S, Borodyansky L and Fruehauf JH: Delivery of RNA interference. Cell Cycle. 5:2103–2109. 2006. View Article : Google Scholar
17	Dave RS and Pomerantz RJ: RNA interference: on the road to an alternate therapeutic strategy! Rev Med Virol. 13:373–385. 2003.PubMed/NCBI
18	Marumoto T, Zhang D and Saya H: Aurora-A - a guardian of poles. Nat Rev Cancer. 5:42–50. 2005. View Article : Google Scholar : PubMed/NCBI
19	Ke YW, Dou Z, Zhang J and Yao XB: Function and regulation of Aurora/Ipl1p kinase family in cell division. Cell Res. 13:69–81. 2003. View Article : Google Scholar : PubMed/NCBI
20	Katayama H, Sasai K, Kawai H, et al: Phosphorylation by Aurora kinase A induces Mdm2-mediated destabilization and inhibition of p53. Nat Genet. 36:55–62. 2004. View Article : Google Scholar : PubMed/NCBI

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Silencing of Aurora kinase A by RNA interference inhibits tumor growth in human osteosarcoma cells by inducing apoptosis and G2/M cell cycle arrest

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