目的·探究GPR87在调节非小细胞肺癌（non-small cell lung cancer，NSCLC）侵袭和迁移中的作用及分子机制。方法·利用生物信息学方法，包括GEO、UALCAN、KM Plotter等多个公共数据库分析平台，筛选与NSCLC侵袭相关的候选基因，并预测基因与NSCLC的临床相关性。收集宜昌市中心人民医院2018年1月—2020年8月收治的80例NSCLC临床样本及对应的临床病理资料，利用免疫组化分析肿瘤组织中GPR87的表达，并对GPR87的临床相关性进行分析。用siRNA-GPR87和pCMV-GPR87-his分别转染人肺腺癌细胞系A549和人肺鳞状细胞癌细胞系SK-MES-1，构建低表达和高表达GPR87的细胞系，运用Transwell实验探究GPR87的表达对NSCLC细胞的迁移、侵袭能力的影响，通过酶联免疫吸附试验（enzyme-linked immunosorbent assay，ELISA）检测细胞培养上清液中MMP7的分泌量，用RT-qPCR检测GPR87、MMP2、MMP7、MMP9、E-cadherin、N-cadherin、vimentin、snail、twist、RHOA、RHOC、ROCK1的mRNA表达水平，用ELISA检测MMP7的蛋白分泌量，用Western blotting检测GPR87、MMP9、E-cadherin、vimentin、RHOA、ROCK1的蛋白表达水平。结果·生信分析和临床样本的数据显示，GPR87 mRNA和蛋白在NSCLC中高表达，且会导致患者临床分期更差、更易发生淋巴结转移，提示GPR87可能是NSCLC高侵袭性的关键基因。GPR87表达下调可显著降低A549和SK-MES-1细胞的侵袭和迁移能力，而过表达GPR87可增强A549和SK-MES-1细胞的侵袭和迁移能力。进一步检测发现，GPR87的下调导致A549和SK-MES-1细胞中MMP2、MMP7、MMP9、RHOA、RHOC和ROCK1的mRNA表达水平，MMP7的蛋白分泌量，MMP9、RHOA、ROCK1的蛋白表达水平降低；过表达GPR87增加了细胞MMP2、MMP7、MMP9、RHOA、RHOC和ROCK1的mRNA表达水平、MMP7的蛋白分泌量、MMP9、RHOA、ROCK1的蛋白表达水平。无论GPR87敲低或者过表达，上皮间质转化相关基因和蛋白的表达均无明显变化。结论·GPR87的高表达与NSCLC的高侵袭性密切相关。在SK-MES-1和A549细胞中，GPR87可通过激活RHOA/ROCK1信号通路，促进MMPs的表达，最终促进NSCLC的侵袭与迁移。

Objective ·To explore the role and molecular mechanism of GPR87 in regulating the invasion and migration of non-small cell lung cancer (NSCLC). Methods ·Bioinformatics methods, including GEO, UALCAN, KM Plotter and other public database analysis platforms, were used to screen candidate genes related to NSCLC invasion and predict their clinical relevance to NSCLC. Eighty NSCLC clinical patient samples and corresponding clinical pathological data were collected from Yichang Central People's Hospital from January 2018 to August 2020. Immunohistochemistry was used to analyze the expression of GPR87 in tumor tissues and the clinical relevance of GPR87 was analyzed. siRNA-GPR87 and pCMV-GPR87-his were transfected into the human lung adenocarcinoma cell line A549 and the human lung squamous cell carcinoma cell line SK-MES-1, to construct cell lines with low and high expression of GPR87. Transwell assay was used to investigate the effect of GPR87 expression on the migration and invasion ability of NSCLC cells. ELISA was used to detect the secretion of MMP7 in the culture supernatant. RT-qPCR was used to detect the mRNA expression levels of GPR87, MMP2, MMP7, MMP9, E-cadherin,N-cadherin, vimentin,snail,twist, RHOA, RHOC, and ROCK1. ELISA was used to detect the secreted protein MMP7. Western blotting was used to detect the protein expression levels ofGPR87, MMP9, E-cadherin, vimentin, RHOA, and ROCK1. Results ·Bioinformatics analysis of clinical sample data showed that GPR87 was highly expressed in NSCLC. Patients with higher expression of GPR87 had worse clinical stage and were more prone to lymph node metastasis, suggesting that GPR87 might be a key gene for the high invasiveness of NSCLC. Downregulation of GPR87 expression significantly reduced the invasion and migration ability of A549 and SK-MES-1 cells, while overexpression of GPR87 enhanced the invasion and migration ability of A549 and SK-MES-1 cells. Further detection revealed that downregulation of GPR87 led to decreased mRNA expression levels of MMP2, MMP7, MMP9, RHOA, RHOC, and ROCK1, as well as a reduction in the secretion of MMP7 and the protein expression levels of MMP9, RHOA, and ROCK1 in A549 and SK-MES-1 cells. Overexpression of GPR87 increased the mRNA expression levels of MMP2, MMP7, MMP9, RHOA, RHOC, and ROCK1, as well as the secretion of MMP7 and the protein expression levels of MMP9, RHOA, and ROCK1. Regardless of GPR87 knockdown or overexpression, the expression of genes and proteins related to epithelial-mesenchymal transition (EMT) in the cells did not change significantly. Conclusion ·High expression of GPR87 is closely related to the high invasiveness of NSCLC. In SK-MES-1 and A549 cells, GPR87 can activate the RHOA/ROCK1 signaling pathway, promote the expression of MMPs, and ultimately promote the invasion and migration of NSCLC.