A novel tRNA-derived small RNA tsRNA-Ile-5-0044 is a candidate biomarker for laryngeal squamous cell carcinoma.

tRNA-derived small RNAs (tsRNAs) have emerged as pivotal regulators and promising biomarkers in multiple malignancies, however their functional roles and clinical significance in HNSCC remain incompletely elucidated. Here, we found tsRNA-Ile-5-0044 was significantly upregulated in HNSCC tissues, notably, survival analysis demonstrated that its prognostic significance was confined to HNSCC and mesothelioma, underscoring its specificity for HNSCC diagnosis and prognosis. qRT-PCR validation confirmed that tsRNA-Ile-5-0044 expression was markedly elevated in both LSCC tissues and plasma, and higher expression of tsRNA-Ile-5-0044 was positively asosiated with advanced TNM stage and tumor size of LSCC patients, indicating its potential as a diagnostic biomarker and progression-related indicator for LSCC. Functional assays showed that knockdown of tsRNA-Ile-5-0044 significantly suppressed the proliferative and colony-forming capacities of LSCC cells. Target gene prediction and enrichment analyses revealed that tsRNA-Ile-5-0044 targeted key oncogenes and tumor asosiated genes (e.g., MYC, TP53, AKT1) and regulated critical signaling pathways. Mechanistically, tsRNA-Ile-5-0044 could target and inhibit TP53 expression in LSCC cells. Collectively, our findings identify tsRNA-Ile-5-0044 as a novel biomarker for the diagnosis and prognosis of LSCC, and uncover its oncogenic role through the regulation of cancer-relevant genes and pathways, thereby offering novel insights into the regulatory landscape of tsRNAs in LSCC.