Long Non-Coding RNA DUXAP8 Facilitates Cell Viability, Migration, and Glycolysis in Non-Small-Cell Lung Cancer via Regulating HK2 and LDHA by Inhibition of miR-409-3p.

PURPOSE

Long non-coding RNAs (lncRNAs) were confirmed to play important roles in human cancers. In this study, we explored the functional role of lncRNA double homeobox A pseudogene 8 (DUXAP8) in non-small-cell lung cancer (NSCLC).

METHODS

Real-time quantitative PCR (RT-qPCR) was used to detect DUXAP8 and microRNA-409-3p (miR-409-3p) expression. CCK-8, cell colony formation assay, and Transwell migration assay were performed to measure cell growth and migration, respectively. The expression of the relative proteins was detected by Western blot. Cell glycolysis was determined by glucose uptake, adenosine triphosphate (ATP) concentration, lactate generation, extracellular acidification rate and oxygen consumption rate assays. Bioinformatics analysis and dual-luciferase reporter assay were used to measure the interaction among DUXAP8, miR-409-3p, hexokinase 2 (HK2) and lactate dehydrogenase A (LDHA). In vivo, subcutaneous tumor formation assay was performed in the nude mice.

RESULTS

DUXAP8 was highly expressed in NSCLC, while miR-409-3p was downregulated. High expression of DUXAP8 was positively related to the grade division and negatively associated with the 5-year survival rate of NSCLC patients. Downregulated DUXAP8 significantly suppressed cell growth, metastasis and glycolysis. Besides, DUXAP8 sponged miR-409-3p to promote HK2 and LDHA expression. DUXAP8 promoted cell viability, migration and glycolysis by regulating miR-409-3p/HK2/LDHA axis. Moreover, DUXAP8 downregulation markedly inhibited tumor growth in vivo.

CONCLUSION

Our findings demonstrated that DUXAP8 served as an oncogene in the progression of NSCLC.