A novel tyrosine tRNA-derived fragment, tRFTyr, induces oncogenesis and lactate accumulation in LSCC by interacting with LDHA.
Cell Mol Biol Lett
; 28(1): 49, 2023 Jun 26.
Article
en En
| MEDLINE
| ID: mdl-37365531
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.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Ácido Láctico
/
Neoplasias de Cabeza y Cuello
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Cell Mol Biol Lett
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2023
Tipo del documento:
Article
País de afiliación:
China