Abstract

Nasopharyngeal cancer (NPC) is a malignant tumor that originates from mucosal epithelial cells of the nasopharynx. As an emerging cancer-associated microRNA, miR-138-5p has been shown to modulate various malignant cell malignancies. However, its precise biological function and regulatory mechanism in NPC remain to be further elucidated. Human NPC cell lines (HK-1 and C666-1) were used for in vitro study, and nude mouse xenograft models were used for in vivo investigations. A bioinformatic method was utilized for the prediction of RNA expression patterns and molecular interactions. RT-qPCR was performed for the detection of miR-138-5p and CENPN expression. Luciferase activity detection and RNA pulldown experiments were used for verification of gene interaction. Flow cytometry and colony formation assays were conducted to evaluate cell cycle distribution, proliferative capacity, and apoptosis rate. Furthermore, extracellular acidification rate, lactate generation, and glucose uptake were assessed to explore the regulatory effects of miR-138-5p and CENPN on glycolysis in NPC cells. Protein levels of CENPN and key molecules associated with cell cycle, apoptosis, glycolysis, and the PI3K signaling pathway were quantified by western blot analysis. CENPN expression is analyzed to be upregulated in head and neck cancer samples, and its high expression is associated with unfavorable clinical prognosis. In NPC cells, miR-138-5p was markedly downregulated and was verified to directly target the 3′ untranslated region of CENPN, thereby negatively regulating its expression. Functionally, overexpressing miR-138-5p obstructed malignant phenotype, glycolysis, and tumor growth of NPC cells, where these inhibitory effects were significantly counteracted by enforced CENPN expression. Moreover, miR-138-5p overexpression inactivated the PI3K/Akt/mTOR signaling by reducing CENPN expression in NPC cells. In conlusion, miR-138-5p inhibits cell growth, glycolysis, and tumorigenesis in NPC