Xu Tianwei, Yan Shuai, Jiang Lihua, Yu Shanxun, Lei Tianyao, Yang Daolu, Lu Binbin, Wei Chenchen, Zhang Erbao, Wang Zhaoxia
Department of Oncology, Cancer Medical Center, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, Jiangsu, P.R. China.
Department of Epidemiology and Biostatistics, Center for Global Health, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing 211100, P.R. China.
Mol Ther Nucleic Acids. 2019 Sep 6;17:405-413. doi: 10.1016/j.omtn.2019.06.008. Epub 2019 Jun 20.
Lung cancer is the most common cancer all around the world, with high morbidity and mortality. Long noncoding RNA (lncRNA) has been reported to have a critical role in non-small-cell lung cancer (NSCLC) proliferation and migration. In the present study, we analyzed The Cancer Genome Atlas (TCGA) data, and we found that lncRNA Small Nucleolar RNA Host Gene 17 (SNHG17) was upregulated in NSCLC driven by the amplification of copy number, indicating the special role of SNHG17 in NSCLC. The full exact length of SNHG17 was determined by rapid amplification of cDNA ends (RACE). We modulated SNHG17 expression by RNAi and a series of functional assays were performed. Flow cytometry was used to explore the involvement of SNHG17 in NSCLC cell apoptosis. Results showed that the knockdown of SNHG17 inhibited the proliferation and migration and promoted the apoptosis of NSCLC cells. We acquired the global gene expression profile regulated by SNHG17 in A549 through RNA sequencing (RNA-seq) assays. We found 637 genes were upregulated while 581 genes were downregulated. We selected three genes (FOXA1, XAF1, and BIK) that were closely related to proliferation and apoptosis, and we confirmed their altered expression in A549 and PC-9 cells treated with small interfering RNA si-SNHG17. Our findings indicated gene amplification-driven lncRNA SNHG17 promotes cell proliferation and migration in NSCLC, suggesting its potential value as a biomarker in NSCLC.
肺癌是全球最常见的癌症，发病率和死亡率都很高。据报道，长链非编码RNA（lncRNA）在非小细胞肺癌（NSCLC）的增殖和迁移中起关键作用。在本研究中，我们分析了癌症基因组图谱（TCGA）数据，发现lncRNA小核仁RNA宿主基因17（SNHG17）在拷贝数扩增驱动的NSCLC中上调，表明SNHG17在NSCLC中的特殊作用。通过cDNA末端快速扩增（RACE）确定了SNHG17的全长。我们通过RNA干扰调节SNHG17的表达，并进行了一系列功能测定。使用流式细胞术探讨SNHG17在NSCLC细胞凋亡中的作用。结果表明，敲低SNHG17可抑制NSCLC细胞的增殖和迁移，并促进其凋亡。我们通过RNA测序（RNA-seq）分析获得了A549中受SNHG17调控的全局基因表达谱。我们发现637个基因上调，581个基因下调。我们选择了三个与增殖和凋亡密切相关的基因（FOXA1、XAF1和BIK），并证实了它们在用小干扰RNA si-SNHG17处理的A549和PC-9细胞中的表达变化。我们的研究结果表明，基因扩增驱动的lncRNA SNHG17促进NSCLC细胞的增殖和迁移，提示其作为NSCLC生物标志物的潜在价值。
