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

Li Wang; Huishan Wang; Bining Wu; Chun Zhang; Hualin Yu; Xueyan Li; Qinjue Wang; Xiaoli Shi; Chengfeng Fan; Dayu Wang; Jing Luo; Jinsong Yang

doi:10.2147/OTT.S273797

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

Onco Targets Ther. 2020 Nov 9:13:11459-11470. doi: 10.2147/OTT.S273797. eCollection 2020.

Authors

Li Wang^#¹, Huishan Wang^#², Bining Wu^#³, Chun Zhang¹, Hualin Yu¹, Xueyan Li¹, Qinjue Wang⁴, Xiaoli Shi⁵, Chengfeng Fan¹, Dayu Wang⁶, Jing Luo⁷, Jinsong Yang¹

Affiliations

¹ Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, People's Republic of China.
² Department of Gastroenterology, Shanghai Songjiang District Central Hospital, Shanghai, People's Republic of China.
³ Respiratory Department, Nanjing Yuhua Hospital, Yuhua Branch of Nanjing First Hospital, Nanjing, People's Republic of China.
⁴ Department of Orthopedics, Nanjing First Hospital, Nanjing Medical University, Nanjing, People's Republic of China.
⁵ Department of Hepatology Surgery, First Affiliated Hospital of Nanjing Medical University, Nanjing, People's Republic of China.
⁶ Department of Obstetrics and Gynecology, Drum Tower Hospital, Medical School of Nanjing University, Nanjing, People's Republic of China.
⁷ Department of Cardiothoracic Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, People's Republic of China.

^# Contributed equally.

Abstract

Background: 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: LINC00551; PKM2; c-Myc; glycolysis; lung adenocarcinoma.

Grants and funding

This research was supported by the Medical Science Development Subject in Science and Technology Project of Nanjing (Grant No. ZKX13017) the Natural Science Foundation of Jiangsu province (No. BK20151086), the National Nature Scientific Foundation of China (No.81673030). National Science Foundation for Natural Youth Grant (No. 81902354).