A novel tyrosine tRNA-derived fragment, tRF^Tyr, induces oncogenesis and lactate accumulation in LSCC by interacting with LDHA

Transfer (t)RNA-derived small RNA (tsRNA), generated from precursor or mature tRNA, is a new type of small non-coding RNA (sncRNA) that has recently been shown to play a vital role in human cancers. However, its role in laryngeal squamous cell carcinoma (LSCC) remains unclear.

We elucidated the expression profiles of tsRNAs in four paired LSCC and non-neoplastic tissues by sequencing and verified the sequencing data by quantitative real-time PCR (qRT-PCR) of 60 paired samples. The tyrosine-tRNA derivative tRF^Tyr was identified as a novel oncogene in LSCC for further study. Loss-of-function experiments were performed to evaluate the roles of tRF^Tyr in tumorigenesis of LSCC. Mechanistic experiments including RNA pull-down, parallel reaction monitoring (PRM) and RNA immunoprecipitation (RIP) were employed to uncover the regulatory mechanism of tRF^Tyr in LSCC.

tRF^Tyr was significantly upregulated in LSCC samples. Functional assays showed that knockdown of tRF^Tyr significantly suppressed the progression of LSCC. A series of mechanistic studies revealed that tRF^Tyr could enhance the phosphorylated level of lactate dehydrogenase A (LDHA) by interacting with it. The activity of LDHA was also activated, which induced lactate accumulation in LSCC cells.

Our data delineated the landscape of tsRNAs in LSCC and identified the oncogenic role of tRF^Tyr in LSCC. tRF^Tyr could promote lactate accumulation and tumour progression in LSCC by binding to LDHA. These findings may aid in the development of new diagnostic biomarkers and provide new insights into therapeutic strategies for LSCC.