Abstract

Larynx cancer, a malignant tumor originating from the epithelial cells of the larynx, remains a significant clinical challenge. Although both N 5 -methylcytosine (m 5 C) modification and glycolysis are critically implicated in cancer progression, their functional interplay in larynx cancer is not well defined. This study aims to elucidate the mechanism through which m 5 C modification influences larynx cancer progression via glycolysis. We performed bioinformatics analysis on the GSE59102 data set to identify m 5 C-related differentially expressed genes (DEGs) between larynx cancer and normal tissues. Functional assays, including CCK-8, EdU staining, glucose uptake, lactate production, and extracellular acidification rate (ECAR) measurements, were conducted to assess cell viability, proliferation, and glycolysis in larynx cancer cell lines (AMC-HN-8 and TU686). The underlying mechanism was further investigated using methylated RNA immunoprecipitation (MeRIP), RNA immunoprecipitation (RIP), and dual-luciferase reporter assays. In vivo validation was obtained through xenograft tumor models and immunohistochemistry. Our results demonstrated that the m 5 C methyltransferase NOP2 was significantly upregulated in larynx cancer. Knockdown of NOP2 inhibited cell viability, proliferation, and glycolysis in larynx cancer cells, and attenuated tumor growth in nude mice. Mechanistically, NOP2 silencing reduced the m 5 C modification on TPI1 mRNA, thereby decreasing its stability. Furthermore, overexpression of TPI1 rescued the impaired glycolysis in larynx cancer cells caused by NOP2 knockdown. In summary, this study reveals that NOP2 facilitates larynx cancer progression by enhancing glycolysis through m 5 C-mediated stabilization of TPI1 mRNA. Our findings uncover the NOP2/m 5 C/TPI1 axis as a novel therapeutic target and provide new insights into RNA methylation-driven metabolic reprogramming in larynx cancer.