LINK-A promotes cell proliferation through the regulation of aerobic glycolysis in non-small-cell lung cancer

Abstract

Wei Zhao,1,2 Wancheng Li,3 Wenjing Dai,3 Na Huang,3 Jing Qiu3 1Department of Clinical Biochemistry, School of Laboratory Medicine, Chengdu Medical College, Chengdu, People’s Republic of China; 2Department of Respiratory Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing, People’s Republic of China; 3Department of Respiratory Medicine, The First Affiliated Hospital of Chengdu Medical College, Chengdu, People’s Republic of China Purpose: Non-small-cell lung cancer (NSCLC) is the one of the most common malignancies worldwide, and occurs at a higher frequency in male individuals. Little is known about the role of the long intergenic noncoding RNA for kinase activation (LINK-A) in NSCLC, so in the present study we assessed its potential role on cell proliferation in NSCLC. Methods: Expression levels of LINK-A in NSCLC tissues and cell lines were detected by quantitative reverse-transcription polymerase chain reaction. LINK-A was knocked down and overexpressed separately in A549 cells and NCI-H1299 cells. The effect of LINK-A expression on cell proliferation was determined by MTT assay. The correlation between LINK-A and hexokinase II (HKII) expression was investigated by Western blot and HKII Activity Assay. Glucose consumption and lactate production assay were used to investigate the aerobic glycolysis in NSCLC cells. The effect of LINK-A in vivo was determined by xenograft assay. Results: LINK-A expression levels were increased in NSCLC tissues compared with normal tissues. Moreover, LINK-A expression was positively correlated with NSCLC clinicopathological characteristics and survival rate, while knockdown of LINK-A reduced NSCLC cell proliferation. LINK-A expression was also positively correlated with HKII, and NSCLC cells with low LINK-A expression were found to have significantly reduced HKII protein expression, accompanied by a reduction in enzyme activity levels. Both in vitro and in vivo experiments showed that LINK-A expression affected glucose consumption and lactate production through regulation of HKII expression. Conclusion: These data suggest that the functions of LINK-A in NSCLC might play a key role in tumor progression and that LINK-A could be a promising predictive biomarker and potential therapeutic target for NSCLC. Keywords: non-small-cell lung cancer, LINK-A, proliferation, hexokinase II, aerobic glycolysis, prognosis

Keywords

• Non-small cell lung cancer ∙ LINK-A ∙ Proliferation ∙ Hexokinase II ∙ Aerobic glycolysis ∙ Prognosis