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

Abstract

Background 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. Methods 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 tRFTyr was identified as a novel oncogene in LSCC for further study. Loss-of-function experiments were performed to evaluate the roles of tRFTyr 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 tRFTyr in LSCC. Results tRFTyr was significantly upregulated in LSCC samples. Functional assays showed that knockdown of tRFTyr significantly suppressed the progression of LSCC. A series of mechanistic studies revealed that tRFTyr 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. Conclusions Our data delineated the landscape of tsRNAs in LSCC and identified the oncogenic role of tRFTyr in LSCC. tRFTyr 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.

tRNA-Derived Small RNAs: A Novel Regulatory Small Noncoding RNA in Renal Diseases

“…These complexes are then transported to the nucleus, enhancing the interaction between EEF1A1 and the MDM2 proto-oncogene (MDM2), ultimately promoting GC progression [ 49 ]. Additionally, Zhao et al [ 50 ] found that the upregulated tRF-Tyr in laryngeal squamous cell carcinoma enhances tumor progression by binding with lactate dehydrogenase A (LDHA), affecting its phosphorylation and leading to increased lactic acid accumulation [ 50 ]. These studies highlight the diverse biological roles of tsRNAs, which involve direct binding to target proteins, formation of complexes for intracellular transport, and regulation of posttranslational modifications.…”