HK2 and LDHA upregulation mediate hexavalent chromium-induced carcinogenesis, cancer development and prognosis through miR-218 inhibition.
Ecotoxicol Environ Saf
; 279: 116500, 2024 Jul 01.
Article
en En
| MEDLINE
| ID: mdl-38795416
ABSTRACT
Hexavalent chromium [Cr(VI)] is one of the most common environmental contaminants due to its tremendous industrial applications, but its effects and mechanism remain to be investigated. Our previous studies showed that Cr(VI) exposure caused malignant transformation and tumorigenesis. This study showed that glycolytic proteins HK2 and LDHA levels were statistically significant changed in blood samples of Cr(VI)-exposed workers and in Cr-T cells compared to the control subjects and parental cells. HK2 and LDHA knockdown inhibited cell proliferation and angiogenesis, and higher HK2 and LDHA expression levels are associated with advanced stages and poor prognosis of lung cancer. We found that miR-218 levels were significantly decreased and miR-218 directly targeted HK2 and LDHA for inhibiting their expression. Overexpression of miR-218 inhibited glucose consumption and lactate production in Cr-T cells. Further study found that miR-218 inhibited tumor growth and angiogenesis by decreasing HK2 and LDHA expression in vivo. MiR-218 levels were negatively correlated with HK2 and LDHA expression levels and cancer development in human lung and other cancers. These results demonstrated that miR-218/HK2/LDHA pathway is vital for regulating Cr(VI)-induced carcinogenesis and human cancer development.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Regulación hacia Arriba
/
Cromo
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MicroARNs
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Carcinogénesis
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Hexoquinasa
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Neoplasias Pulmonares
Límite:
Animals
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Humans
Idioma:
En
Revista:
Ecotoxicol Environ Saf
Año:
2024
Tipo del documento:
Article
País de afiliación:
China