A novel tRNA-derived fragment tRF-Val-CAC-008 as a diagnostic biomarker and pyroptosis regulator in LSCC
Hongxia Deng1, Dong Ye1, Shijie Qiu2
1Department of Otolaryngology-Head and Neck Surgery, The Affiliated LiHuili Hospital of Ningbo University, Ningbo 315040 Zhejiang, China.
Objective:
Laryngeal cancer is one of the most common malignant tumors of the head and neck, with laryngeal squamous cell carcinoma (LSCC) being the most significant pathological type. Transfer RNA-derived fragments (tRFs) fragments have been implicated in tumor progression through diverse regulatory mechanisms. This study examined the diagnostic value and role of tRF-Val-CAC-008 in LSCC.
Methods:
Levels of tRF-Val-CAC-008 were quantified in LSCC tissues, plasma, saliva, and cells using real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). The diagnostic value of tRF-Val-CAC-008 was then assessed using the receiver operating characteristic (ROC) curve. LSCC cells were transfected with mimics or inhibitors of tRF-Val-CAC-008, which increased or decreased its level accordingly. Cell proliferation was evaluated using EdU and the cell counting kit-8 (CCK-8) assays. The level of lactate dehydrogenase (LDH) in LSCC cells was measured using an LDH release assay. Pyroptosis-associated proteins were analyzed by Western blotting (WB).
Results:
tRF-Val-CAC-008 exhibited significantly higher expression levels in LSCC tissues, plasma and saliva. This higher expression correlated with its pro-proliferative effects and suppression of pyroptosis observed in vitro. In LSCC cells, tRF-Val-CAC-008 mimics promoted cell proliferation and reduced LDH secretion. The expression of gasdermin E (GSDME) and caspase-3 proteins was also decreased by tRF-Val-CAC-008 mimics, which in turn regulated pyroptosis. The ROC curves suggest that combined plasma and saliva tRF-Val-CAC-008 can serve as a diagnostic marker to distinguish LSCC patients from healthy participants.
Conclusions:
The study concluded that tRF-Val-CAC-008 could act as a diagnostic marker for LSCC; it promotes tumor growth by suppressing pyroptosis and promoting cell proliferation.
