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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. 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.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Kim DJ,Jang JH,Ham SY,Choi SH,Park SS,Jeong SY,Kim BC,Jeon DY,Lee BJ,Ko BK,Park JW,Cho WJ

doi

10.1016/j.bbrc.2019.11.106

subject

Has Abstract

pub_date

2020-02-05 00:00:00

pages

402-407

issue

2

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(19)32232-6

journal_volume

522

pub_type

杂志文章

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