TY - JOUR
T1 - RNA N6-methyladenosine demethylase FTO regulates PD-L1 expression in colon cancer cells
AU - Tsuruta, Nobuhiro
AU - Tsuchihashi, Kenji
AU - Ohmura, Hirofumi
AU - Yamaguchi, Kyoko
AU - Ito, Mamoru
AU - ariyama, hiroshi
AU - Kusaba, Hitoshi
AU - Akashi, Koichi
AU - Baba, Eishi
N1 - Funding Information:
This work was supported by Japan Society for the Promotion of Science KAKENHI Grant Number 20K07638 (K.T.) and in part by the Yakult Bio-Science Foundation and the Bayer Academic Support Foundation in Japan (H.K.).
Publisher Copyright:
© 2020
PY - 2020/9/10
Y1 - 2020/9/10
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85088877026&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85088877026&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2020.06.153
DO - 10.1016/j.bbrc.2020.06.153
M3 - Article
C2 - 32828292
AN - SCOPUS:85088877026
SN - 0006-291X
VL - 530
SP - 235
EP - 239
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 1
ER -
