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

被引:27
作者
Jiang, Zhenhuan [1 ,2 ]
Jiang, Jiannong [2 ]
Yang, Huilin [1 ]
Ge, Zhijun [3 ]
Wang, Qiang [2 ]
Zhang, Leiyan [2 ]
Wu, Chenguang [2 ]
Wang, Jinzhi [4 ]
机构
[1] Soochow Univ, Affiliated Hosp 1, Dept Orthopaed, Suzhou 215006, Jiangsu, Peoples R China
[2] Peoples Hosp Yixing City, Dept Orthopaed, Yixing 214200, Jiangsu, Peoples R China
[3] Peoples Hosp Yixing City, Dept Anesthesiol, Yixing 214200, Jiangsu, Peoples R China
[4] Soochow Univ, Sch Med, Dept Cell Biol, Suzhou 215123, Jiangsu, Peoples R China
基金
中国国家自然科学基金;
关键词
osteosarcoma; Aurora kinase A; tumorigenicity; RNA interference; lentivirus; GENE-THERAPY; OVEREXPRESSION; CANCER; EXTREMITIES; EXPRESSION; CARCINOMA;
D O I
10.3892/or.2014.2986
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:1249 / 1254
页数:6
相关论文
共 21 条
[1]  
Abdelrahim Maen, 2006, J RNAi Gene Silencing, V2, P136
[2]   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 [J].
Bacci, Gaetano ;
Ferrari, Stefano ;
Mercuri, Mario ;
Longhi, Alessandra ;
Fabbri, Nicola ;
Galletti, Stefano ;
Forni, Cristiana ;
Balladelli, Alba ;
Serra, Massimo ;
Picci, Piero .
ACTA ORTHOPAEDICA, 2007, 78 (03) :377-384
[3]   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].
Bielack, SS ;
Kempf-Bielack, B ;
Delling, G ;
Exner, GU ;
Flege, S ;
Helmke, K ;
Kotz, R ;
Salzer-Kuntschik, M ;
Werner, M ;
Winkelmann, W ;
Zoubek, A ;
Jürgens, H ;
Winkler, K .
JOURNAL OF CLINICAL ONCOLOGY, 2002, 20 (03) :776-790
[4]   LYMPHOCYTE GENE-THERAPY [J].
CULVER, KW ;
ANDERSON, WF ;
BLAESE, RM .
HUMAN GENE THERAPY, 1991, 2 (02) :107-109
[5]   RNA interference: on the road to an alternate therapeutic strategy! [J].
Dave, RS ;
Pomerantz, RJ .
REVIEWS IN MEDICAL VIROLOGY, 2003, 13 (06) :373-385
[6]  
DORFMAN HD, 1995, CANCER, V75, P203, DOI 10.1002/1097-0142(19950101)75:1+<203::AID-CNCR2820751308>3.0.CO
[7]  
2-V
[8]   On the role of aurora-A in centrosome function [J].
Dutertre, S ;
Descamps, S ;
Prigent, C .
ONCOGENE, 2002, 21 (40) :6175-6183
[9]  
Gritsko TM, 2003, CLIN CANCER RES, V9, P1420
[10]   Phosphorylation by aurora kinase A induces Mdm2-mediated destabilization and inhibition of p53 [J].
Katayama, H ;
Sasai, K ;
Kawai, H ;
Yuan, ZM ;
Bondaruk, J ;
Suzuki, F ;
Fujii, S ;
Arlinghaus, RB ;
Czerniak, BA ;
Sen, S .
NATURE GENETICS, 2004, 36 (01) :55-62