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Alpha-fetoprotein upregulates hepatocellular carcinoma cell-intrinsic PD-1 expression through the LATS2/YAP/TEAD1 pathway.
- Source :
-
Biochimica et biophysica acta. General subjects [Biochim Biophys Acta Gen Subj] 2024 May; Vol. 1868 (5), pp. 130592. Date of Electronic Publication: 2024 Feb 21. - Publication Year :
- 2024
-
Abstract
- Background: Hepatocellular carcinoma (HCC) cell-intrinsic programmed death 1 (PD-1) promotes tumor progression. However, the mechanisms that regulate its expression are unclear. This study investigated the impact of alpha-fetoprotein (AFP) on HCC cell-intrinsic PD-1 expression.<br />Methods: The expression of PD-1 and AFP at the gene and protein levels was detected using real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) and western blotting (WB). Proteins interacting with AFP were examined by co-immunoprecipitation (CO-IP). Chromatin immunoprecipitation (ChIP) and dual luciferase reporter assays were used to identify transcription-enhanced association domain 1 (TEAD1) binding to the promoter of PD-1.<br />Results: The expression of HCC cell-intrinsic PD-1 was positively correlated with AFP. Mechanistically, AFP inhibited the phosphorylation of large tumor suppressor 2 (LATS2) and yes-associated protein (YAP). As a result, YAP is transferred to the nucleus and forms a transcriptional complex with TEAD1, promoting PD-1 transcription by binding to its promoter.<br />Conclusion: AFP is an upstream regulator of the HCC cell-intrinsic PD-1 and increases PD-1 expression via the LATS2/YAP/TEAD1 axis.<br />General: Our findings provide insight into the mechanisms of HCC development and offer new ideas for further in-depth studies of HCC.<br />Competing Interests: Declaration of competing interest The authors declare no conflicts of interest regarding the publication of this paper.<br /> (Copyright © 2024 Elsevier B.V. All rights reserved.)
- Subjects :
- Humans
alpha-Fetoproteins metabolism
Programmed Cell Death 1 Receptor metabolism
Transcription Factors genetics
Transcription Factors metabolism
Adaptor Proteins, Signal Transducing genetics
Adaptor Proteins, Signal Transducing metabolism
Protein Serine-Threonine Kinases genetics
Tumor Suppressor Proteins genetics
Tumor Suppressor Proteins metabolism
TEA Domain Transcription Factors
Carcinoma, Hepatocellular metabolism
Liver Neoplasms metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1872-8006
- Volume :
- 1868
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Biochimica et biophysica acta. General subjects
- Publication Type :
- Academic Journal
- Accession number :
- 38395204
- Full Text :
- https://doi.org/10.1016/j.bbagen.2024.130592