Targeting TRMT5 suppresses hepatocellular carcinoma progression via inhibiting the HIF-1α pathways / 浙江大学学报(英文版)(B辑:生物医学和生物技术)
Journal of Zhejiang University. Science. B
;
(12): 50-63, 2023.
Artículo
en Inglés
| WPRIM
| ID: wpr-971468
ABSTRACT
Accumulating evidence has confirmed the links between transfer RNA (tRNA) modifications and tumor progression. The present study is the first to explore the role of tRNA methyltransferase 5 (TRMT5), which catalyzes the m1G37 modification of mitochondrial tRNAs in hepatocellular carcinoma (HCC) progression. Here, based on bioinformatics and clinical analyses, we identified that TRMT5 expression was upregulated in HCC, which correlated with poor prognosis. Silencing TRMT5 attenuated HCC proliferation and metastasis both in vivo and in vitro, which may be partially explained by declined extracellular acidification rate (ECAR) and oxygen consumption rate (OCR). Mechanistically, we discovered that knockdown of TRMT5 inactivated the hypoxia-inducible factor-1 (HIF-1) signaling pathway by preventing HIF-1α stability through the enhancement of cellular oxygen content. Moreover, our data indicated that inhibition of TRMT5 sensitized HCC to doxorubicin by adjusting HIF-1α. In conclusion, our study revealed that targeting TRMT5 could inhibit HCC progression and increase the susceptibility of tumor cells to chemotherapy drugs. Thus, TRMT5 might be a carcinogenesis candidate gene that could serve as a potential target for HCC therapy.
Texto completo:
Disponible
Índice:
WPRIM (Pacífico Occidental)
Asunto principal:
ARNt Metiltransferasas
/
Transducción de Señal
/
Hipoxia de la Célula
/
Regulación Neoplásica de la Expresión Génica
/
Carcinoma Hepatocelular
/
Línea Celular Tumoral
/
Subunidad alfa del Factor 1 Inducible por Hipoxia
/
Neoplasias Hepáticas
Límite:
Humanos
Idioma:
Inglés
Revista:
Journal of Zhejiang University. Science. B
Año:
2023
Tipo del documento:
Artículo
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