Unveiling the immunological functions of the RNA m5C reader YBX1 in cancer

Y-box binding protein 1 (YBX1) is a multifunctional RNA-binding protein that plays a central role in cancer progression across diverse tumor types. Mechanistically, YBX1 promotes tumorigenesis through multiple pathways, including interactions with long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) to regulate gene transcription and translation, direct protein-protein interactions to stabilize oncogenic factors or facilitate their nuclear translocation, and recognition of RNA modifications such as m⁵C to enhance mRNA stability and translation. Beyond intrinsic tumor cell functions, YBX1 also modulates the tumor immune microenvironment. It can regulate immune cell activity and the efficacy of immune checkpoint inhibitors in both m⁵C-dependent and -independent manners, thereby influencing responses to immunotherapy. Collectively, YBX1 acts as a critical driver of cancer progression and therapeutic resistance, integrating epitranscriptomic regulation, RNA-protein interactions, and immune modulation. These insights highlight YBX1 as a promising biomarker and potential target for combination therapies in cancer treatment.