Zhong Ning, Shi Shunbin, Wang Hongzhen, Wu Guangzhou, Wang Yunliang, Ma Qiang, Wang Hongwei, Liu Yuanhua, Wang Jinzhi
Department of Thoracic Surgery, Kunshan First People's Hospital Affiliated to Jiangsu University, Kunshan, Jiangsu, P.R. China.
Department of Thoracic Surgery, Affiliated Wujiang Hospital of Nantong Uinversity, Wujiang, Jiangsu, P.R. China.
Int J Oncol. 2016 Sep;49(3):1028-38. doi: 10.3892/ijo.2016.3605. Epub 2016 Jul 5.
Aurora kinase A (AURKA) is an oncogenic serine/threonine kinase, it plays important roles in tumorigenesis and chemoresistance. In this study, we investigated the expression of AURKA in lung adenocarcinoma tissues, the role of small interference RNA targeting AURKA on growth, cell cycle, and apoptosis of lung adenocarcinoma cell lines in vitro. The AURKA is highly expressed in lung adenocarcinoma tissues and human lung adenocarcinoma cell lines. Lentivirus-mediated short hairpin RNA (shRNA) was used to knock down AURKA expression in human lung adenocarcinoma cell lines H1299 and A549. The results indicated that depletion of AURKA could inhibit cell growth, cause cell cycle arrest and apoptosis. The potential mechanisms of AURKA inhibition induced cell cycle arrest and apoptosis are associated with downregulated RAF-1, CCND2, CCND3, CDK4, PAK4, EGFR and upregulated WEE1 expression. Furthermore, AURKA knockdown cooperated with vincristine (VCR) to repress A549 cell proliferation. Therefore, AURKA plays important roles in the proliferation of human lung adenocarcinoma cells, which suggests that AURKA could be a promising tool for lung adenocarcinoma therapy.
极光激酶A(AURKA)是一种致癌性丝氨酸/苏氨酸激酶,在肿瘤发生和化疗耐药中发挥重要作用。在本研究中,我们调查了AURKA在肺腺癌组织中的表达,以及靶向AURKA的小干扰RNA对肺腺癌细胞系体外生长、细胞周期和凋亡的作用。AURKA在肺腺癌组织和人肺腺癌细胞系中高表达。采用慢病毒介导的短发夹RNA(shRNA)敲低人肺腺癌细胞系H1299和A549中AURKA的表达。结果表明,AURKA的缺失可抑制细胞生长,导致细胞周期停滞和凋亡。AURKA抑制诱导细胞周期停滞和凋亡的潜在机制与RAF-1、CCND2、CCND3、CDK4、PAK4、EGFR表达下调以及WEE1表达上调有关。此外,AURKA敲低与长春新碱(VCR)协同抑制A549细胞增殖。因此,AURKA在人肺腺癌细胞增殖中起重要作用,这表明AURKA可能是肺腺癌治疗的一个有前景的靶点。