RNA N6-methyladenosine demethylase FTO regulates PD-L1 expression in colon cancer cells

Nobuhiro Tsuruta, Kenji Tsuchihashi, Hirofumi Ohmura, Kyoko Yamaguchi, Mamoru Ito, Hiroshi Ariyama, Hitoshi Kusaba, Koichi Akashi, Eishi Baba

Research output: Contribution to journalArticle

Abstract

Fat mass and obesity-associated protein (FTO) is an enzyme that demethylates N6-methyladenosine (m6A), the most abundant RNA modifications in a cell. The upregulated expression of FTO promotes the progression of various types of cancer by modulating cell-intrinsic genes which relate to malignant potential. However, the impact of FTO on the expression of immune-checkpoint molecules in the tumor cells, which are important for immune escape, has not been well understood. We examined the relevance of FTO to programmed cell death-ligand 1 (PD-L1) expression in colon cancer cells. HCT-116 cells showed high expression of both FTO and PD-L1 proteins. The knockdown of FTO by small interfering RNA decreased mRNA and protein levels of PD-L1 in HCT-116 cells. To elucidate the underlying mechanism by which FTO regulates the expression of PD-L1, we depleted FTO in HCT-116 in the presence of IFN-γ, which is a major stimulus to upregulate PD-L1 expression. Depletion of FTO reduced PD-L1 expression in an IFN-γ signaling-independent manner. RNA immunoprecipitation assay revealed the m6A modification of the PD-L1 mRNA and the binding of FTO to the PD-L1 mRNA in HCT-116. Taken together, our results indicated that FTO could regulate PD-L1 expression in colon cancer cells and provides new insights into the regulation of PD-L1 expression by RNA modification.

Original languageEnglish
Pages (from-to)235-239
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume530
Issue number1
DOIs
Publication statusPublished - Sep 10 2020

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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