RMND5A upregulation via IGF2BP3-mediated mA RNA modification enhances malignant traits and immune evasion in laryngeal squamous cell carcinoma cells.

N6-methyladenosine (mA) is the most prevalent mRNA internal modification in eukaryotic mRNAs and is frequently associated with progression and immune response in human cancers. This study delves into the function of mA reader insulin like growth factor 2 mRNA binding protein 3 (IGF2BP3) in the immune evasion and progression of laryngeal squamous cell carcinoma (LSCC), along with its underpinning mechanisms. We conducted integrated bioinformatics to examine mA-modifying regulators and their prognostic values in LSCC. IGF2BP3 was identified as a promising candidate, which was verified to be highly expressed in LSCC tissues and cell lines. Furthermore, the aberrant IGF2BP3 upregulation in the context of LSCC was found to be partly ascribed to DNA hypomethylation. IGF2BP3 was found to elevate RMND5A expression in an mA-dependent manner. Silencing either IGF2BP3 or RMND5A significantly decreased the viability, colony formation ability, and tumorigenicity of LSCC cells. Moreover, this intervention reduced the protein level of PD-L1 in cells while increasing CD8 T cell infiltration in xenograft tumors. However, further upregulation of RMND5A negated the tumor-suppressive and immune-enhancing effects observed upon IGF2BP3 silencing. In conclusion, this study demonstrates that IGF2BP3 elevates RMND5A expression through mA modification, thereby promoting malignant properties and immune evasion in LSCC cells.