非小细胞肺癌（NSCLC）是最常见的肺癌类型，预后较差。基于分子机制鉴定生物标志物对于肺癌的早期诊断、及时治疗和改善预后至关重要。MALAT1在NSCLC中已被报道具有过表达和促肿瘤功能。它被提议作为癌症的潜在生物标志物，用于诊断和预后。因此，本研究旨在根据NSCLC细胞系中MALAT1表达的调控概况，通过对差异表达基因（DEGs）的生物信息学分析来探究相关性。我们使用RT-qPCR测量了MALAT1的表达水平。通过细胞计数、胶萼形成、伤口愈合和转入室侵袭实验分析了MALAT1在NSCLC中的生物功能。此外，通过转录组测序分析了针对MALAT1敲低的基因表达谱，并通过GO和KEGG通路富集分析了MALAT1调控的差异表达基因。我们使用生物信息学数据库进行基因表达和总体生存分析。与MRC5细胞（正常肺细胞系）相比较的结果显示，NSCLC细胞中MALAT1的表达显著较高。MALAT1敲低可降低三种NSCLC细胞系的细胞存活、增殖、迁移和侵袭。NSCLC细胞中的RNA测序分析显示，198个基因上调，266个基因下调由MALAT1敲低引起。利用OncoLnc数据库对这些共同差异表达基因进行生存分析，选择了五个差异表达基因，磷酸甘油酸变位酶1（PGAM1）、磷酸甘油酸变位酶4（PGAM4）、核仁蛋白6（NOL6）、核小体组装蛋白1类似物5（NAP1L5）和sestrin1（SESN1）。对这些选定差异表达基因的基因表达水平进行了TNMplot数据库的基因表达分析。MALAT1可能作为一个增强NSCLC细胞存活、增殖、胶萼形成和侵袭的肿瘤基因。RNA测序和生物信息学分析结果表明，PGAM1、PGAM4、NOL6、NAP1L5和SESN1与患者的生存和肿瘤发生密切相关。我们相信，进一步研究这五个差异表达基因将为了解MALAT1在NSCLC中的致癌作用提供有价值的信息。© 2023. BioMed Central Ltd., part of Springer Nature.

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer and has a poor prognosis. Identifying biomarkers based on molecular mechanisms is critical for early diagnosis, timely treatment, and improved prognosis of lung cancer. MALAT1 has been reported to have overexpressed and tumor-promoting functions in NSCLC. It has been proposed as a potential biomarker for the diagnosis and prognosis of cancer. Therefore, this study was conducted to profile the changes in gene expression according to the regulation of expression of MALAT1 in NSCLC cell lines and to investigate the correlation through bioinformatic analysis of differentially expressed genes (DEGs).MALAT1 expression levels were measured using RT-qPCR. The biological functions of MALAT1 in NSCLC were analyzed by cell counting, colony forming, wound-healing, and Transwell invasion assays. In addition, gene expression profiling in response to the knockdown of MALAT1 was analyzed by transcriptome sequencing, and differentially expressed genes regulated by MALAT1 were performed by GO and KEGG pathway enrichment analyses. Bioinformatic databases were used for gene expression analysis and overall survival analysis.Comparative analysis versus MALAT1 expression in MRC5 cells (a normal lung cell line) and the three NSCLC cell lines showed that MALAT1 expression was significantly higher in the NSCLC cells. MALAT1 knockdown decreased cell survival, proliferation, migration, and invasion in all three NSCLC cell lines. RNA-seq analysis of DEGs in NSCLC cells showed 198 DEGs were upregulated and 266 DEGs downregulated by MALAT1 knockdown in all three NSCLC cell lines. Survival analysis on these common DEGs performed using the OncoLnc database resulted in the selection of five DEGs, phosphoglycerate mutase 1 (PGAM1), phosphoglycerate mutase 4 (PGAM4), nucleolar protein 6 (NOL6), nucleosome assembly protein 1 like 5 (NAP1L5), and sestrin1 (SESN1). The gene expression levels of these selected DEGs were proved to gene expression analysis using the TNMplot database.MALAT1 might function as an oncogene that enhances NSCLC cell survival, proliferation, colony formation, and invasion. RNA-seq and bioinformatic analyses resulted in the selection of five DEGs, PGAM1, PGAM4, NOL6, NAP1L5, and SESN1, which were found to be closely related to patient survival and tumorigenesis. We believe that further investigation of these five DEGs will provide valuable information on the oncogenic role of MALAT1 in NSCLC.© 2023. BioMed Central Ltd., part of Springer Nature.