Tristetraprolin regulates phagocytosis through interaction with CD47 in head and neck cancer

Won Hyeok Lee; Song Hee Kim; Jae Hee An; Tae-Koon Kim; Hee Jeong Cha; Hyo Won Chang; Sang Yoon Kim; Seong Who Kim; Myung Woul Han

doi:10.3892/etm.2022.11478

Tristetraprolin regulates phagocytosis through interaction with CD47 in head and neck cancer

Exp Ther Med. 2022 Jun 29;24(3):541. doi: 10.3892/etm.2022.11478. eCollection 2022 Sep.

Authors

Won Hyeok Lee¹, Song Hee Kim¹, Jae Hee An¹, Tae-Koon Kim¹, Hee Jeong Cha², Hyo Won Chang³, Sang Yoon Kim³, Seong Who Kim⁴, Myung Woul Han¹

Affiliations

¹ Department of Otolaryngology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan 44033, Republic of Korea.
² Department of Pathology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan 44033, Republic of Korea.
³ Department of Otolaryngology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea.
⁴ Department of Biochemistry and Molecular Biology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea.

Abstract

CD47 is expressed in all human cancer cells, including head and neck cancer, and initiates a signaling cascade to inhibit macrophage phagocytosis. However, the mechanism underlying CD47 overexpression has not been elucidated in radioresistant head and neck cancer. The present study demonstrated that decreased Tristetraprolin (TTP) expression induced a sustained overexpression of CD47 using reverse transcription-quantitative PCR and western blotting, and that CD47 overexpression prevented phagocytosis using a phagocytosis assay in a radioresistant HN31R cell line. Subsequently, using TTP transfection, RNA interference, duel-luciferase assay and EMSA, it was revealed that TTP transfection enhanced phagocytosis through degradation of CD47 mRNA by directly binding to CD47 AREs within the CD47 3'UTR. Based on our previous study, methylation-specific PCR and western blotting revealed that DNMT1 was overexpressed in radioresistant HN31R cell line and TTP expression was decreased epigenetically by DMNT1 associated DNA methylation. Overall, these findings provided novel insight into the role of TTP as a biomarker of CD47-positive head and neck cancer patients.

Keywords: AU-rich elements; CD47; DNA methyltransferase; head and neck cancer; phagocytosis; post-transcriptional modification; radioresistance; tristetraprolin.

Grants and funding

Funding: This work was supported by the National Research Foundation (NRF) grant funded by the Korea government (MSIT grant nos. MRC-2018R1A5A2020732, NRF-2020R1A2C1011879, NRF-2019R1A2C1006788 and NRF-2021R1A2C1010046) and Ulsan University Hospital Research Grant (grant no. UUH -2020-06).