SNF5 promotes cell proliferation and immune evasion in non-small cell lung cancer

Immune evasion is the process that tumor cells accelerate growth and metastasis by evading the recognition and attack of immune cells. SNF5 is one of the core subunits of SWI/SNF, which is involved in the development of a variety of malignancies. However, the functions of SNF5 in Non-Small Cell Lung Cancer (NSCLC) and the mechanism of SNF5 regulates immune evasion are still unclear. Based on this, we analyzed the expression of SNF5 and overall survival of lung cancer tissues through the cancer genome atlas (TCGA) database. Then we performed genetic gain and loss of function experiments with SNF5 using lentivirus infection and siRNA in NSCLC A549 and NCI-H1299 cells, respectively. We investigated the proliferation and immune evasion of these cells. We further explored the mechanism of SNF5 on NSCLC cells immune evasion. Our data showed that SNF5 was significantly increased in lung cancer tissues than that in normal lung tissues. Furthermore, SNF5 promoted NSCLC cells proliferation and the expressions of immune evasion-related genes. Meantime, overexpressed SNF5 reduced mortality of A549 cells when co-cultured with T cells. Moreover, SNF5 regulated the immune evasion by activating the signal transducer and activator of transcription (STAT3)/ phospho-STAT3 pathway in NSCLC cells. Together, our results validate SNF5 as a tumor oncogene and provide a new target for NSCLC treatment.免疫逃逸是肿瘤细胞通过躲避免疫细胞的识别与攻击，从而加速自身生长与转移的过程。SNF5是SWI/SNF的核心亚基之一，参与多种恶性肿瘤的发生发展。然而，SNF5在非小细胞肺癌（Non-Small Cell Lung Cancer, NSCLC）中的功能及其调控免疫逃逸的分子机制仍未明确。基于此，我们通过癌症基因组图谱（Cancer Genome Atlas, TCGA）数据库分析了肺癌组织中SNF5的表达水平以及患者的总生存期。随后我们分别在非小细胞肺癌A549与NCI-H1299细胞中，采用慢病毒感染与小干扰RNA（small interfering RNA, siRNA）技术开展SNF5的功能获得与功能缺失实验，其中A549细胞使用慢病毒感染法，NCI-H1299细胞使用小干扰RNA技术。我们对这些细胞的增殖能力与免疫逃逸能力进行了检测分析，并进一步探究了SNF5调控非小细胞肺癌细胞免疫逃逸的分子机制。本研究数据显示，肺癌组织中SNF5的表达水平显著高于正常肺组织。此外，SNF5可促进非小细胞肺癌细胞的增殖以及免疫逃逸相关基因的表达。同时，当与T细胞共培养时，过表达SNF5可降低A549细胞的死亡率。此外，SNF5可通过激活非小细胞肺癌细胞中的信号转导与转录激活因子（Signal Transducer and Activator of Transcription, STAT3）/磷酸化STAT3（phospho-STAT3）通路，调控细胞免疫逃逸。综上，本研究证实SNF5可作为癌基因，为非小细胞肺癌的治疗提供了全新的靶点。