Long Noncoding RNA LINC00551 Suppresses Glycolysis and Tumor Progression by Regulating c-Myc-Mediated PKM2 Expression in Lung Adenocarcinoma

Abstract

Li Wang,1,* Huishan Wang,2,* Bining Wu,3,* Chun Zhang,1 Hualin Yu,1 Xueyan Li,1 Qinjue Wang,4 Xiaoli Shi,5 Chengfeng Fan,1 Dayu Wang,6 Jing Luo,7 Jinsong Yang1 1Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, People’s Republic of China; 2Department of Gastroenterology, Shanghai Songjiang District Central Hospital, Shanghai, People’s Republic of China; 3Respiratory Department, Nanjing Yuhua Hospital, Yuhua Branch of Nanjing First Hospital, Nanjing, People’s Republic of China; 4Department of Orthopedics, Nanjing First Hospital, Nanjing Medical University, Nanjing, People’s Republic of China; 5Department of Hepatology Surgery, First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China; 6Department of Obstetrics and Gynecology, Drum Tower Hospital, Medical School of Nanjing University, Nanjing, People’s Republic of China; 7Department of Cardiothoracic Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jinsong YangDepartment of Oncology, Nanjing First Hospital, Nanjing Medical University, 68 Changle Road, Nanjing City, Jiangsu Province, People’s Republic of ChinaTel [phone]Fax [phone]Email [email protected] LuoDepartment of Cardiothoracic Surgery, Jinling Hospital, Medical School of Nanjing University, 305 East Zhongshan Road, Nanjing City, Jiangsu Province, People’s Republic of ChinaTel [phone]Email [email protected]: Lung adenocarcinoma (LUAD) is a leading cause of mortality associated with cancer globally. Thus, it is essential to elucidate its tumorigenesis and prognosis. Accumulating evidence shows that long noncoding RNAs (lncRNAs) play important roles in the occurrence and progression of tumors by regulating their glucose metabolism.Methods: Bioinformatics analysis was performed to explore the expression of LINC00551 in LUAD. The level of LINC00551 in LUAD cells and tissues was detected by RT-qPCR. CCK-8, colony formation, EDU and transwell assays were conducted to evaluate the cell growth and migration of LUAD cells (A549 and PC9). High throughput sequencing was used to discover the downstream genes of LINC00551. The metabolic function of LUAD cells was identified by glucose uptake and lactate production assays. Furthermore, tumor xenografts were established to investigate the effects of LINC00551 on tumor growth in vivo.Results: Herein, we found that LINC00551 was low-expressed in LUAD, and its level correlated with clinical prognosis. Ectopic expression of LINC00551 inhibited the proliferation and migration of LUAD cells (A549 and PC9). High throughput sequencing and gene enrichment analysis revealed that LINC0551 may be involved in metabolic pathway. Glucose uptake and lactate production assays suggested that LINC00551 suppressed glycolysis of LUAD cells. Mechanistically, our work revealed that LINC00551 inhibited glycolysis in LUAD cells by impairing c-Myc-mediated transcription of an important glycolysis-related enzyme PKM2.Conclusion: In summary, our study identifies LINC00551 as a tumor suppressor in LUAD and implicates the LINC00551/c-Myc/PKM2 axis in the glycolytic remodeling of LUAD.Keywords: lung adenocarcinoma, LINC00551, c-Myc, PKM2, glycolysis

Keywords

• lung adenocarcinoma
• linc00551
• c-myc
• pkm2
• glycolysis