Doxorubicin inhibits PD-L1 expression by enhancing TTP-mediated decay of PD-L1 mRNA in cancer cells
- PMID: 31767150
- DOI: 10.1016/j.bbrc.2019.11.106
Doxorubicin inhibits PD-L1 expression by enhancing TTP-mediated decay of PD-L1 mRNA in cancer cells
Abstract
Recent research revealed that doxorubicin (DOX) decreased expression of programmed death-ligand 1 (PD-L1) in cancer cells. However, the detailed mechanisms underlying this effect are not well established. Here, we demonstrate that doxorubicin down-regulates PD-L1 expression through induction of AU-rich element (ARE) binding protein tristetraprolin (TTP) in cancer cells. PD-L1 mRNA contain three AREs within its 3'UTR. Doxorubicin induced expression of TTP, increased TTP binding to the 3rd ARE of the PD-L1 3'UTR, and increased decay of PD-L1 mRNA. Inhibition of TTP abrogates the inhibitory effect of doxorubicin on PD-L1 expression VSports手机版. Our data suggest that TTP plays a key role in doxorubicin-mediated down-regulation of PD-L1 by enhancing degradation of PD-L1 mRNA in cancer cells. .
Keywords: Cancer cells; Doxorubicin; PD-L1; Tristetraprolin; mRNA decay. V体育安卓版.
Copyright © 2019 Elsevier Inc. All rights reserved V体育ios版. .
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