Liang Zongying, Yu Qian, Ji Hongtao, Tian Dali
Department of Thoracic Surgery, The Fourth Affiliated Hospital of China Medical University, Shenyang, Liaoning 110032, P.R. China.
Department of Thoracic Surgery, The Affiliated Hospital of Chengde Medical College, Chengde, Hebei 067000, P.R. China.
Exp Ther Med. 2019 Apr;17(4):3195-3202. doi: 10.3892/etm.2019.7302. Epub 2019 Feb 22.
Lung cancer is a leading cause of cancer-associated mortality and morbidity worldwide. Previous studies have suggested that ATP-binding cassette transporter E1 (ABCE1) acetylation is upregulated in the tissues and cells of lung cancer and is associated with the prognosis of patients with lung cancer. The aim of the present study was to investigate the association between Tat interactive protein 60 kDa (Tip60) expression and ABCE1 acetylation, and the effect of Tip60 on the biological functions of A549 lung carcinoma cells. The expression levels of Tip60 and ABCE1 acetylation were examined using western blot and co-immunoprecipitation (Co-IP) assays in normal bronchial epithelial (HBE) and human lung cancer (A549) cells. The expression of Tip60 then was downregulated in A549 cells using small interfering RNA. Wound healing and Transwell assays were used to assess cell invasion and migration. The biological effects of Tip60 in lung cancer cells were investigated using MTT and flow cytometric assays. Subsequently, tumor xenografts were established to observe the effect of Tip60 on lung cancer . Western blot and Co-IP assays were performed to investigate the mechanism of Tip60 in A549 cells. Tip60 expression and ABCE1 acetylation were upregulated in the lung cancer cells compared with the normal bronchial epithelial cells. Downregulation of Tip60 decreased the acetylation of ABCE1 and inhibited cell proliferation, invasion and migration. Furthermore, the downregulation of Tip60 activated the apoptotic pathway in order to achieve its suppressive function. In the xenografts, the tumor weight and volume were notably reduced due to the downregulation of Tip60 expression. The results of the present study strongly suggest that Tip60 is a novel target in the prevention and treatment of lung cancer.
肺癌是全球癌症相关死亡率和发病率的主要原因。先前的研究表明，ATP结合盒转运蛋白E1（ABCE1）的乙酰化在肺癌组织和细胞中上调，并且与肺癌患者的预后相关。本研究的目的是探讨60 kDa Tat相互作用蛋白（Tip60）表达与ABCE1乙酰化之间的关联，以及Tip60对A549肺癌细胞生物学功能的影响。使用蛋白质免疫印迹法和免疫共沉淀（Co-IP）分析法检测正常支气管上皮（HBE）细胞和人肺癌（A549）细胞中Tip60的表达水平以及ABCE1的乙酰化情况。然后，使用小干扰RNA下调A549细胞中Tip60的表达。采用伤口愈合实验和Transwell实验评估细胞侵袭和迁移能力。使用MTT实验和流式细胞术检测Tip60对肺癌细胞的生物学作用。随后，建立肿瘤异种移植模型以观察Tip60对肺癌的影响。通过蛋白质免疫印迹法和免疫共沉淀实验研究Tip60在A549细胞中的作用机制。与正常支气管上皮细胞相比，肺癌细胞中Tip60的表达和ABCE1的乙酰化上调。Tip60表达下调可降低ABCE1的乙酰化水平，并抑制细胞增殖、侵袭和迁移。此外，Tip60表达下调激活凋亡途径以实现其抑制功能。在异种移植模型中，由于Tip60表达下调，肿瘤重量和体积显著减小。本研究结果强烈表明，Tip60是肺癌预防和治疗的新靶点。
