| Literature DB >> 31767150 |
Dong Jun Kim1, Ji Hun Jang1, Soo-Youn Ham2, Seong Hee Choi1, Sung Soon Park1, So Yeon Jeong1, Beom Chang Kim1, Do Yong Jeon1, Byung Ju Lee1, Byung Kyun Ko3, Jeong Woo Park4, Wha Ja Cho5.
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. 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.Entities:
Keywords: Cancer cells; Doxorubicin; PD-L1; Tristetraprolin; mRNA decay
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Year: 2019 PMID： 31767150 DOI： 10.1016/j.bbrc.2019.11.106
Source DB: PubMed Journal: Biochem Biophys Res Commun ISSN： 0006-291X Impact factor: 3.575