c-Met up-regulates the expression of PD-L1 through MAPK/NF-κBp65 pathway.
J Mol Med (Berl)
; 100(4): 585-598, 2022 04.
Article
em En
| MEDLINE
| ID: mdl-35122106
ABSTRACT
Sorafenib acquired drug resistance during the treatment of hepatocellular carcinoma (HCC) reduces the efficacy of the drug. The immune escape effect induced by PD-L1 is largely associated with drug resistance of HCC. However, the regulated mechanism of PD-L1 is unclear. This research aimed to clarify the control mechanism of PD-L1. c-Met was found abnormally highly expressed in Huh-7SR with high PD-L1 expression. In addition, c-Met, as the upstream target molecule of PD-L1, promoted the proliferation and migration of HCC in vitro and in vivo. We also found that c-Met activated the MAPK signaling pathway and the downstream NF-κBp65 transcription factor, which interacts with the proximal region of the PD-L1 promoter to promote PD-L1 expression. In conclusion, c-Met regulates the transcription of PD-L1 through the MAPK/NF-κBp65 pathway, thereby promoting the progress of HCC. The role of c-Met and PD-L1 in HCC needs to be further studied, but it is a potential target for the treatment of HCC. KEY MESSAGES In the study, it was found that c-Met is also abnormally highly expressed in Huh-7SR with high PD-L1 expression and can promote the development of HCC in vitro and in vivo. PD-L1 and c-Met expression levels are positively correlated. In the follow-up mechanism study, we found that c-Met activated the MAPK signaling pathway and subsequently activated the downstream NF-κBp65 transcription factor, which interacts with the proximal region of the PD-L1 promoter to promote PD-L1 expression. Our study found that c-Met regulates the transcription of PD-L1 through the MAPK/NF-κBp65 pathway, thereby promoting the progress of HCC.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Carcinoma Hepatocelular
/
Neoplasias Hepáticas
Limite:
Humans
Idioma:
En
Revista:
J Mol Med (Berl)
Assunto da revista:
BIOLOGIA MOLECULAR
/
GENETICA MEDICA
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
China