Jiang Zhenhuan, Jiang Jiannong, Yang Huilin, Ge Zhijun, Wang Qiang, Zhang Leiyan, Wu Chenguang, Wang Jinzhi
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.
Oncol Rep. 2014 Mar;31(3):1249-54. doi: 10.3892/or.2014.2986. Epub 2014 Jan 20.
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.
丝氨酸/苏氨酸激酶家族成员极光激酶A(AURKA)在多种人类癌症中均有过表达现象。然而,AURKA在骨肉瘤(OS)(最常见的原发性骨恶性肿瘤类型)中的作用尚未明确。我们使用AURKA特异性慢病毒传递短发夹RNA(shRNA),显著且持续地沉默了人OS细胞SAOS-2和U2OS中的内源性AURKA表达。我们发现,OS细胞中AURKA的下调显著降低了其体外集落形成能力和体内致瘤能力。我们通过MTT法进一步评估了AURKA沉默对细胞活力的影响,并通过流式细胞仪检测评估了细胞凋亡和细胞周期。结果表明,AURKA沉默通过诱导OS细胞凋亡和G2/M期细胞周期阻滞来抑制细胞活力。综上所述,我们的研究结果表明,AURKA通过抑制细胞凋亡和推动细胞周期对OS生长起着关键作用。通过慢病毒传递特异性shRNA抑制AURKA显示出治疗骨肉瘤的潜在疗效。