文献类型：期刊文献

英文题名：Alpha-fetoprotein upregulates hepatocellular carcinoma cell-intrinsic PD-1 expression through the LATS2/YAP/TEAD1 pathway

作者：Leng, Guangxian[1];Gong, Hongxia[2];Liu, Guiyuan[1,3];Kong, Yin[1,4];Guo, Liuqing[1];Zhang, Youcheng[1]

第一作者：Leng, Guangxian

通信作者：Zhang, YC[1]

机构：[1]Lanzhou Univ, Hosp 2, Dept Gen Surg, Lanzhou 730030, Gansu Province, Peoples R China;[2]Gansu Univ Tradit Chinese Med, Prov Level Key Lab Mol Med Major Dis & Study Preve, Lanzhou 730000, Gansu Province, Peoples R China;[3]Chongqing Three Gorges Med Higher Specialized Sch, Dept Cardiol, Peoples Hosp, Chongqing 404100, Peoples R China;[4]Lanzhou Univ, Dept Hepatol, Hosp 2, Lanzhou 730030, Gansu Province, Peoples R China

第一机构：Lanzhou Univ, Hosp 2, Dept Gen Surg, Lanzhou 730030, Gansu Province, Peoples R China

通信机构：[1]corresponding author), Lanzhou Univ, Hosp 2, Dept Gen Surg, Lanzhou 730030, Gansu Province, Peoples R China.

年份：2024

卷号：1868

期号：5

外文期刊名：BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS

收录：;Scopus(收录号：2-s2.0-85186750448);WOS:【SCI-EXPANDED(收录号:WOS:001195666700001)】；

基金：We thank the Doctoral Students Training Research Fund of Lanzhou University Second Hospital (YJS-BD-32) and National Natural Science Foundation of China (82060800) for Funding this study.

语种：英文

外文关键词：AFP; HCC; LATS2; TEAD1; Tumor cell-intrinsic PD-1; YAP

摘要：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. 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. 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. Conclusion: AFP is an upstream regulator of the HCC cell-intrinsic PD-1 and increases PD-1 expression via the LATS2/YAP/TEAD1 axis. General: Our findings provide insight into the mechanisms of HCC development and offer new ideas for further in-depth studies of HCC.