Doxorubicin inhibits miR-140 expression and upregulates PD-L1 expression in HCT116 cells, opposite to its effects on MDA-MB-231 cells

Noel Mopouguini Naba, Nazife Tolay, Batu Erman, Ayca Sayi Yazgan*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)

Abstract

One of the most challenging problems in colorectal cancer (CRC) is resistance to chemotherapy drugs such as doxorubicin (DOX). The programmed death ligand-1 (PD-L1) is related to chemoresistance and is overexpressed in several human cancer cell types. Here, we investigated the changes in the expression of PD-L1 in DOX-treated CRC and breast cancer (BRC) cells. Also, to address PD-L1 regulation, we assessed expression levels of miR-140 and miR-34a, two microRNAs that can target the 3’ UTR region of the gene encoding PD-L1. HCT116 CRC and MDA-MB-231 BRC cells were treated with various doses of DOX in culture and PD-L1 expression was quantified using qRT-PCR, flow cytometry, and western blot analysis. We also evaluated PD-L1 localization in HCT116 cells by immunofluorescence. Next, we assessed expression of miR-140 and miR-34a in DOX-treated HCT116 and MDA-MB-231 cells. Finally, we investigated whether miR-140 targets the 3’ UTR of the gene encoding PD-L1 in HCT116 cells using the p2FP-RNAi RNAi reporter vector system. PD-L1 expression in HCT116 cells, while low at baseline, can be induced by treatment with 0.5 µM DOX. MDA-MB-231 baseline PD-L1 expression exceeded HCT116 cell maximal expression and decreased following DOX treatment. We further demonstrated that PD-L1 localizes to the cell surface in DOX-treated HCT116 cells. While miR-140 expression decreased in DOX-treated HCT116 cells, it increased in DOX-treated MDA-MB-231 cells. MiR-34a expression increased in both DOX-treated cell types. Finally, we present evidence for the regulation of PD-L1 by miR-140 in HCT116 cells. PD-L1 expression can increase following treatment with DOX in HCT116 cells but decrease in MDA-MB-231 cells, suggesting a distinct response to DOX in these two different cancer types. Also, a negative correlation between PD-L1 and miR-140 was observed in DOX-treated HCT116 cells, but not in MDA-MB-231 cells.

Original languageEnglish
Pages (from-to)15-23
Number of pages9
JournalTurkish Journal of Biology
Volume44
Issue number1
DOIs
Publication statusPublished - 2020

Bibliographical note

Publisher Copyright:
© TÜBİTAK.

Keywords

  • Doxorubicin
  • MiR-140
  • MiR-34a
  • PD-L1

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