RNA 5‐Methylcytosine Regulator NSUN3 promotes tumor progression through regulating immune infiltration in head and neck squamous cell carcinoma

Abstract Objective This study aimed to determine whether the RNA, 5‐methylcytosine (m5C), is involved in the progression of head and neck squamous cell carcinoma (HNSCC). Materials and methods We used least absolute shrinkage and selection operator to establish a prognostic score (PS) model based on the m5C regulator expression. Immune scores were calculated using the estimation of stromal and immune cells in malignant tumor tissues using expression data. The biological functions of the m5C regulator, NOP2/Sun RNA methyltransferase 3 (NSUN3), were thoroughly investigated in vitro and in vivo. Results The PS model acted as efficient prognostic factors in HNSCC. The expression of NSUN3, with the maximum weight, was found to be upregulated and indicated a poor prognosis. Meanwhile, NSUN3 knockdown inhibited the tumor proliferation and growth both in vitro and in vivo. High PS status was negatively correlated with CD8 + T, γδ + T, and M1 macrophage percentages. NSUN3 knockdown increased the infiltration of M1 macrophages but decreased the percentage of M2 macrophages. Conclusions The PS index is a novel and promising biomarker for predicting the prognosis and immune infiltration microenvironment in HNSCC. Moreover, NSUN3 plays a key role in this process and may serve as a potential therapeutic target for HNSCC.