PMID- 32565935 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20200928 IS - 1792-1074 (Print) IS - 1792-1082 (Electronic) IS - 1792-1074 (Linking) VI - 20 IP - 1 DP - 2020 Jul TI - Ubiquitin-specific peptidase 17 promotes cisplatin resistance via PI3K/AKT activation in non-small cell lung cancer. PG - 67-74 LID - 10.3892/ol.2020.11568 [doi] AB - The suppression of ubiquitin-specific peptidase 17 (USP17) has previously been found to result in reduced tumorigenesis and invasion of non-small cell lung cancer (NSCLC) cells. However, the functions and underlying mechanisms of USP17 in NSCLC progression remain unclear. In the present study, cisplatin treatment was found to upregulate USP17 expression in a dose-dependent manner. Furthermore, USP17-overexpressing (USP17-OE) NSCLC A549 and H1299 cells were generated for mechanistic studies. The results from the Cell Counting Kit-8 assay revealed increased cell proliferation in USP17-OE cells compared with that of control cells. Moreover, the viability of USP17-OE cells was significantly higher than that of the control cells, when treated with cisplatin. The results of the biochemical studies demonstrated enhanced PI3K and AKT phosphorylation in USP17-OE NSCLC cells, whereas USP17-knockdown decreased these levels of phosphorylation. By contrast, an AKT inhibitor abolished the USP17-mediated enhancement of proliferation. Moreover, suppression of USP17 or the combination of the AKT inhibitor and cisplatin significantly reduced cell viability. Overall, the results of the present study suggest that PI3K/AKT activation is the underlying mechanism of USP17-mediated cisplatin resistance in NSCLC. CI - Copyright: (c) Zhang et al. FAU - Zhang, Shengchao AU - Zhang S AD - Department of Thoracic Surgery, Qingpu Branch Zhongshan Hospital, Fudan University, Shanghai 201700, P.R. China. FAU - Xu, Zhenglang AU - Xu Z AD - Department of Thoracic Surgery, Qingpu Branch Zhongshan Hospital, Fudan University, Shanghai 201700, P.R. China. FAU - Yuan, Jun AU - Yuan J AD - Department of Thoracic Surgery, Qingpu Branch Zhongshan Hospital, Fudan University, Shanghai 201700, P.R. China. FAU - Chen, Hao AU - Chen H AD - Department of Thoracic Surgery, Qingpu Branch Zhongshan Hospital, Fudan University, Shanghai 201700, P.R. China. LA - eng PT - Journal Article DEP - 20200423 PL - Greece TA - Oncol Lett JT - Oncology letters JID - 101531236 PMC - PMC7286115 OTO - NOTNLM OT - AKT inhibitor OT - cisplatin OT - non-small cell lung cancer OT - ubiquitin-specific peptidase 17 EDAT- 2020/06/23 06:00 MHDA- 2020/06/23 06:01 PMCR- 2020/04/23 CRDT- 2020/06/23 06:00 PHST- 2018/11/08 00:00 [received] PHST- 2019/11/22 00:00 [accepted] PHST- 2020/06/23 06:00 [entrez] PHST- 2020/06/23 06:00 [pubmed] PHST- 2020/06/23 06:01 [medline] PHST- 2020/04/23 00:00 [pmc-release] AID - OL-0-0-11568 [pii] AID - 10.3892/ol.2020.11568 [doi] PST - ppublish SO - Oncol Lett. 2020 Jul;20(1):67-74. doi: 10.3892/ol.2020.11568. Epub 2020 Apr 23.