piR-164552 promotes malignant progression in head and neck squamous cell carcinoma via the RBM4/EIF4E2 signaling axis: Insights from multi-omics and functional analyses
Head and neck squamous cell carcinoma (HNSCC) is a highly aggressive malignancy with limited options for early diagnosis and poor clinical outcomes. In the present study, PIWI-interacting RNA (piR)-164552 was identified as a novel oncogenic regulator in HNSCC. piR-164552 was found to be markedly upregulated in tumor tissues and serum exosomes and its expression promoted the proliferation, migration, invasion and tumorigenicity of HNSCC cells both in vitro and in vivo. Mechanistic analyses revealed that piR-164552 interacted with RNA-binding motif protein 4 (RBM4) and positively regulated RBM4 protein levels, which in turn enhanced the expression of eukaryotic initiation factor 4E-like 2 (EIF4E2), forming a piR-164552/RBM4/EIF4E2 axis. Integrated transcriptomic and translatomic profiling further demonstrated that this axis orchestrated extensive reprogramming of mRNA metabolism, ribosome biogenesis and cancer-associated signaling pathways, underscoring its multilayered role in tumor progression. The present findings highlighted the diagnostic potential of piR-164552 and uncovered its key contribution to the molecular network driving HNSCC, providing new insights into biomarker development and therapeutic strategies.