Cancer Management and Research (Aug 2020)
LncRNA SNHG9 is Downregulated in Non-Small Cell Lung Cancer and Suppressed miR-21 Through Methylation to Promote Cell Proliferation
Abstract
Dingxue Wang,1,* Xiaoqing Cao,2,* Yi Han,2 Daping Yu2 1Department of Oncology, The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, 550001, People’s Republic of China; 2Department of Thoracic Surgery, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing 101149, People’s Republic of China*These authors contributed equally to this workCorrespondence: Daping YuDepartment of Thoracic SurgeryBeijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Area 1st, No. 9 Compound, Beiguan Street, Tongzhou District, Beijing 101149, People’s Republic of ChinaEmail [email protected]: LncRNA SNHG9 has been shown to be an oncogenic lncRNA in glioblastoma, while its role in other cancers is unknown. The aim of this study was to investigate the role of SNHG9 in non-small cell lung cancer (NSCLC).Methods: The differential expression of SNHG9 in NSCLC was first explored by analyzing the TCGA dataset, followed by measuring the expression levels of SNHG9 in paired NSCLC and non-tumor tissues by RT-qPCR. Expression of miR-21 was also determined by RT-qPCR. Correlations were analyzed by linear regression. The interaction between miR-21 and SNHG9 was detected using RNA pull-down. The expression relationship between SNHG9 and miR-21 was analyzed by SNHG9 or miR-21 overexpression experiments. The effects of overexpression of SNHG9 on the methylation of miR-21 were analyzed by methylation-specific PCR (MSP). Cell proliferation was evaluated by CCK-8 assay.Results: By analyzing the TCGA dataset, we observed downregulation of SNHG9 in NSCLC, which was confirmed by measuring the expression levels of SNHG9 in paired NSCLC tumor tissues and non-tumor tissues from NSCLC patients involved in this study. MiR-21 was upregulated in NSCLC tumor tissues and inversely correlated with SNHG9 in cancer tissues but not in non-tumor tissues. The interaction between SNHG9 and miR-21 was predicted by bioinformatic analyses, which was further verified by RNA pull-down. In NSCLC cells, overexpression of SNHG9 led to downregulated miR-21 and increased methylation of miR-21 gene. In contrast, miR-21 did not affect the expression of SNHG9. In addition, overexpression of SNHG9 attenuated the enhancing effects of miR-21 on NSCLC proliferation.Conclusion: SNHG9 might downregulate miR-21 through methylation to suppress cancer cell proliferation.Keywords: SNHG9, non-small cell lung cancer, miR-21, methylation
