Abstract 4451: Elevated USP22 is a potential therapeutic target for human non-small cell lung cancer

Elevated ubiquitin-specific protease 22 (USP22) is associated with enhanced malignancy, therapeutic resistance, and poor prognosis of various human cancers. In this study, the clinicopathological significance of USP22, therapeutic implication of targeting USP22, and underlying molecules of USP22 knockdown were investigated in human non-small cell lung cancer (NSCLC). Immunohistochemistry analysis revealed that USP22 protein was dramatically elevated in ~ 67% of 197 NSCLC tissues compared with adjacent normal lung tissues. Importantly, statistical analysis demonstrated that elevated USP22 was positively associated with advanced cancer stage and a trend to poor prognosis of NSCLC patients. Moreover, siRNA-mediated knockdown of USP22 induced a cell cycle arrest in G1/S phase and significantly suppressed cell proliferation and soft agar colony formations in NSCLC cell lines. In addition, knockdown of USP22 significantly enhanced cisplatin-induced genotoxic effects in NSCLC cell lines. Furthermore, USP22 silencing substantially down-regulated SIRT1 and upregulated p53 tumor suppressor in NSCLC cells, indicating downregulation of USP22 may boost p53-mediated tumor suppression and DNA damage response in NSCLC cells. Knockdown of USP22 also increased global histone H2B monoubiquitylation, H3K4 and H3K79 trimethylation leading to global gene expression profile changes in these NSCLC cells. These results suggest that targeting USP22 will have broad anti-cancer effects via altering multiple cancer signaling pathways. Taken together, data of this study further indicate that the elevated USP22 may potentially represent a prognostic factor and therapeutic target for NSCLC patients. Note: This abstract was not presented at the meeting. Citation Format: Keqiang Zhang, Tommy R Tong, Xinwei Yun, Rebecca Nelson, Nardi Isaac, Ravi Salgia, Dan Raz. Elevated USP22 is a potential therapeutic target for human non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4451. doi:10.1158/1538-7445.AM2017-4451