Tryptophan As a New Member of RNA-Induced Silencing Complexes Prevents Colon Cancer Liver Metastasis.
Adv Sci (Weinh)
; 11(31): e2307937, 2024 Aug.
Article
em En
| MEDLINE
| ID: mdl-39031551
ABSTRACT
Essential amino acids (EAA) and microRNAs (miRs) control biological activity of a cell. Whether EAA regulates the activity of miR has never been demonstrated. Here, as proof-of-concept, a tryptophan (Trp, an EAA) complex containing Argonaute 2 (Ago2) and miRs including miR-193a (Trp/Ago2/miR-193a) is identified. Trp binds miR-193a-3p and interacts with Ago2. Trp/Ago2/miR-193a increases miR-193a-3p activity via enhancing Argonaute 2 (Ago2) RNase activity. Other miRs including miR-103 and miR-107 in the Trp complex enhance miR-193a activity by targeting the same genes. Mechanistically, the Trp/Ago2/miR-193a complex interacts with Trp-binding pockets of the PIWI domain of Ago2 to enhance Ago2 mediated miR activity. This newly formed Ago2/Trp/miR-193a-3p complex is more efficient than miR-193a-3p alone in inhibiting the expression of targeted genes and inhibiting colon cancer liver metastasis. The findings show that Trp regulates miR activity through communication with the RNA-induced silencing complexes (RISC), which provides the basis for tryptophan based miR therapy.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Triptofano
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Neoplasias do Colo
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Complexo de Inativação Induzido por RNA
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MicroRNAs
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Proteínas Argonautas
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Neoplasias Hepáticas
Limite:
Animals
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Humans
Idioma:
En
Revista:
Adv Sci (Weinh)
Ano de publicação:
2024
Tipo de documento:
Article