肺癌是最常见的恶性肿瘤之一，其中约80%的肺癌为非小细胞肺癌。肺癌相关基因的研究一直是国内外学者关注的热点，但迄今为止，肺癌的发生和发展机制尚未完全阐明。我们前期研究发现USP22与癌细胞的增殖有着密切的关系，结合文献学习，我们认为"USP22可能参与p33ING1b和p53的相互作用，其可能通过去泛素化p33ING1b进而参与p53的调控，抑制非小细胞肺癌细胞的增殖"。本研究拟在非小细胞肺癌A549和NCI-H460细胞系中证实USP22与p33ING1b和p53的相互作用，并通过临床样本收集和检测分析，明确USP22、p33ING1b和p53在非小细胞肺癌患者中表达的相关性。从体内和体外两个方面证实USP22在非小细胞肺癌细胞增殖中的作用，尝试从USP22参与p33ING1b和p53的调控作用方面阐述促进非小细胞肺癌细胞增殖的分子机制，为非小细胞肺癌的诊断和治疗提供理论依据与实践基础。

Lung cancer is one of the most commonly seen malignant tumors worldwide, about 80% of which is non-small cell lung cancer (NSCLC). The genes associated with lung cancer have always been a focus of research home and abroad. However, by now the carcinoginesis of lung cancer remains to be fully elucidated.Our initial study found that there were close relations between USP22 and the multiplying of cancer cells. With the study of literatures, we considered that USP22 may be involved in the interactions between p33ING1band p53, which also may participate in the regulation of p53 by deubiquitination p33ING1b, and inhibit the cell proliferation of NSCLC. This research aims to demonstrate the interactions between USP22 with p33ING1b and p53 in the NSCLC cell line A549. We will also assess the relationship of USP22, p33ING1b and p53 using clinical samples of NSCLC. We will confirm the effect of USP22 on NSCLC cell proliferation in vivo and in vitro, and make attempt to elucidate the molecular mechanism by which USP22 modulates p33ING1b and p53, and subsequently promotes NSCLC cells proliferation. We hope this study will provide theory and practical evidences for future diagnosis and treatment of NSCLC.

USP22是一种泛素特异肽酶，属于DUBs家族。目前认为USP22是癌死亡标签之一，并且它与癌的增殖、侵袭转移和治疗预后相关。在本项研究中，我们从体外、体内两方面研究了USP22在人非小细胞肺癌（NSCLC）肿瘤发生中的作用及潜在的作用机制。研究结果表明，USP22在人NSCLC组织和细胞株中呈高表达；USP22基因沉默在体外抑制了NSCLC细胞的生长，引起NSCLC细胞凋亡和细胞周期停滞在G0/G1期；在体内，USP22沉默抑制了裸鼠体内肿瘤的生长。而且，USP22能通过与MDMX相互作用继而激活p53通路，还能通过去泛素化作用调节COX-2继而增强PGE2的表达，发挥促癌作用。USP22可能为NSCLC的治疗提供新靶点。