Work

METTL14 Regulates the Expression of Genes Related to Interferon, Interleukin and MHC Class I in Nasopharyngeal Carcinoma Cells

Year: 2025

Type: article

Abstract: BACKGROUND: Nasopharyngeal carcinoma (NPC), highly prevalent in southern China, often leads to treatment failure in advanced stages due to recurrence or metastasis. While METTL14 plays a crucial role in cancer, its regulation of immune- and inflammation-related genes remains poorly understood. This study aims to investigate whether METTL14 is involved in regulating the expression of genes associated with tumor necrosis factor (TNF), interferon (IFN), interleukin (IL), and MHC class I in NPC cells. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting were used to examine METTL14 expression in NPC cells with either shMETTL14 knockdown or METTL14 overexpression. RNA sequencing was performed to identify differentially expressed genes associated with TNF, IFN, IL, and MHC class I in NPC cells, and qRT-PCR was used to validate the expression of these genes. A cytokine production assay was conducted to measure the levels of TNFSF9, IFI16, IL-6, IL-7, CXCL10, and HLA-B. RESULTS: Our study demonstrates that METTL14 potentially plays a fundamental role in modulating the expression of genes associated with TNF, IFN, IL, and MHC class I in NPC cells. RNA sequencing of NPC cells showed that METTL14 upregulated or downregulated several genes associated with immunity and inflammation, including TNF, IFN, IL, and MHC class I. RNA interference-mediated knockdown of METTL14 revealed its regulatory effects on TNF-related genes (e.g., TNFRSF12A, TNFRSF9, TNFSF15), IFN-induced genes (e.g., PSMC6, PSMD1, PSMA2, PSMA3, PSMB2), and IL-related genes (e.g., CCL5, IL1B, IL32, IL7R, IL6, IL7, CXCL2). Furthermore, METTL14 was found to positively regulate MHC class I gene expression (e.g., HLA-A, -B, -C, -E, -F) in NPC cells. CONCLUSIONS: These findings demonstrate, for the first time, that METTL14 modulates the expression of genes related to TNF, IFN, IL, and MHC class I in NPC, proposing a novel role for METTL14 in linking inflammation with cancer, a function that has not been fully elucidated.

Source: Cancer Medicine

DOI: 10.1002/cam4.71371