Tip60‑siRNA regulates ABCE1 acetylation to suppress lung cancer growth via activation of the apoptotic signaling pathway

Liang,Zongying; Yu,Qian; Ji,Hongtao; Tian,Dali

doi:10.3892/etm.2019.7302

Tip60‑siRNA regulates ABCE1 acetylation to suppress lung cancer growth via activation of the apoptotic signaling pathway

Authors:
- Zongying Liang
- Qian Yu
- Hongtao Ji
- Dali Tian
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Affiliations: Department of Thoracic Surgery, The Fourth Affiliated Hospital of China Medical University, Shenyang, Liaoning 110032, P.R. China
Published online on: February 22, 2019 https://doi.org/10.3892/etm.2019.7302
Pages: 3195-3202

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Abstract

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 in vivo. 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.

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