TY - JOUR AB - Lung cancer is a devastating cancer with high morbidity and mortality. Ubiquitin‑specific protease (USP) is a type of deubiquitinating enzyme (DUB) that has been implicated in numerous cancers, including colorectal, myeloma and breast. In the present study, the expression of USP51 was determined in the lung cancer cell line A549 and cisplatin (also known as DDP)‑resistant lung cancer strain A549/DDP. The expression of zinc‑finger E‑box binding homeobox 1 (ZEB1), a transcriptional repressor, was also examined. The effects of USP51 knockdown or overexpression on proliferation and apoptosis, as well as the impact of ZEB1 overexpression and USP51 interference on apoptosis and ubiquitination were then assessed. Notably, increased expression of USP51 and ZEB1 in A549/DDP cells was observed, and treatment with DDP significantly inhibited proliferation in A549/DDP cells. In addition, knockdown of USP51 in A549/DDP cells significantly induced apoptosis, decreased ZEB1 expression and increased cleaved poly ADP‑ribose polymerase 1 (PARP1) and cleaved caspase‑3 levels. Consistently, USP51 overexpression in A549 cells displayed the opposite effects and potently attenuated DDP‑induced apoptosis. Notably, overexpression of ZEB1 in A549/DDP cells potently attenuated the effects of USP51 knockdown on apoptosis, and co‑IP experiments further demonstrated interaction between USP51 and ZEB. Lastly, knockdown of USP51 promoted ZEB1 ubiquitination, leading to ZEB1 degradation. Collectively, the present findings demonstrated that USP51 inhibition attenuated DDP resistance in A549/DDP cells via ubiquitin‑mediated degradation of ZEB1. Hence, targeting USP51 may serve as a novel therapeutic target for DDP resistance in lung cancer. AD - Department of Respiratory Medicine, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China Department of Respiratory Medicine, QingPu Branch of Zhongshan Hospital Affiliated to Fudan University, Shanghai 201700, P.R. China AU - Zhou,Feng AU - Du,Chunling AU - Xu,Donghui AU - Lu,Jinchang AU - Zhou,Lei AU - Wu,Chaomin AU - Wu,Bo AU - Huang,Jianan DA - 2020/08/01 DO - 10.3892/mmr.2020.11188 EP - 1390 IS - 2 JO - Mol Med Rep KW - ubiquitin‑specific protease zinc‑finger E‑box binding homeobox 1 lung cancer cisplatin resistance apoptosis PY - 2020 SN - 1791-2997 1791-3004 SP - 1382 ST - Knockdown of ubiquitin‑specific protease 51 attenuates cisplatin resistance in lung cancer through ubiquitination of zinc‑finger E‑box binding homeobox 1 T2 - Molecular Medicine Reports TI - Knockdown of ubiquitin‑specific protease 51 attenuates cisplatin resistance in lung cancer through ubiquitination of zinc‑finger E‑box binding homeobox 1 UR - https://doi.org/10.3892/mmr.2020.11188 VL - 22 ER -