@Article{096504021X16280937554409,
AUTHOR = {Dong Li, Fei-fan Sun, Dan Wang,Tao Wang, Jing-jing Peng, Jian-Qiong Feng, Hua Li, Chao Wang, Dai-jun Zhou, Hong Luo, Zeng-qiang Fu, Tao Zhang},
TITLE = {Programmed Death Ligand-1 (PD-L1) Regulated by NRF-2/MicroRNA-1  Regulatory Axis Enhances Drug Resistance and Promotes Tumorigenic  Properties in Sorafenib-Resistant Hepatoma Cells},
JOURNAL = {Oncology Research},
VOLUME = {28},
YEAR = {2020},
NUMBER = {7-8},
PAGES = {827--828},
URL = {http://www.techscience.com/or/v28n7-8/48474},
ISSN = {1555-3906},
ABSTRACT = {Sorafenib, a multityrosine kinase inhibitor, is a standard treatment for advanced hepatocellular carcinoma 
(HCC), but the clinical response to sorafenib is seriously limited by drug resistance. Programmed death ligand-1 
(PD-L1) is one of the most important inhibitory molecules involved in tumor immune evasion. Recently, it 
has been reported that PD-L1 could play crucial roles in drug resistance of many kinds of cancers. However, 
the expression, function, and regulation of PD-L1 in sorafenib-resistant hepatoma cells remain unclear. In this 
study, we reported that PD-L1 was overexpressed in sorafenib-resistant hepatoma cells, and shRNA-mediated 
PD-L1 depletion attenuated drug resistance and suppressed the migration, invasion, colony formation, and 
tumorigenesis in sorafenib-resistant hepatoma cells in vitro and in vivo. Mechanistic investigations indicated 
that loss of microRNA-1 (miR-1), a tumor-suppressive microRNA, contributed to the PD-L1 upregulation in 
sorafenib-resistant hepatoma cells, and PD-L1 was a direct regulatory target of miR-1. Further study revealed 
that an oncogenic transcriptional factor, nuclear factor E2-related factor 2 (NRF-2), was induced in sorafenibresistant hepatoma cells and inhibited expression of miR-1 in vitro. From molecular mechanism insight back 
to the functional verification, we eventually demonstrated that miR-1 executed its tumor-suppressive effects on 
drug resistance and other malignant properties in sorafenib-resistant hepatoma cells partially by PD-L1 inhibition 
in vitro and in vivo. In conclusion, our data suggested that a NRF-2/miR-1/PD-L1 regulatory axis contributed 
to the development and maintenance of drug resistance and other tumorigenic properties in sorafenib-resistant 
hepatoma cells and provided a potential therapeutic target for overcoming sorafenib resistance in HCC.},
DOI = {10.3727/096504021X16280937554409}
}