https://doi.org/10.4081/ejh.2024.4048

Identification of mechanism of the oncogenic role of FGFR1 in papillary thyroid carcinoma

Vol. 68 No. 3 (2024)
Submitted: 16 April 2024
Accepted: 3 July 2024
Published: 22 July 2024
Papillary thyroid carcinoma, FGFR1, deubiquitination, transcription factor, inhibitors
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Authors

Xiong Bing Li
Department of Oncology, Xianning Central Hospital, The First Affiliated Hospital of Hubei University of Science and Technology, Xianning, China.
Jia Li Li
Department of Endocrinology, Xianning Central Hospital, The First Affiliated Hospital of Hubei University of Science and Technology, Xianning, China.
Chao Wang
Department of Oncology, Xianning Central Hospital, The First Affiliated Hospital of Hubei University of Science and Technology, Xianning, China.
Yong Zhang
Department of Oncology, Xianning Central Hospital, The First Affiliated Hospital of Hubei University of Science and Technology, Xianning, China.
Jing Li
lijing316013329@163.com
https://orcid.org/0009-0006-4451-9332
Department of Nephrology, Xianning Central Hospital, The First Affiliated Hospital of Hubei University of Science and Technology, Xianning, China.

Papillary thyroid carcinoma (PTC) is the most prevalent malignancy of the thyroid. Fibroblast growth factor receptor 1 (FGFR1) is highly expressed in PTC and works as an oncogenic protein in this disease. In this report, we wanted to uncover a new mechanism that drives overexpression of FGFR1 in PTC. Analysis of FGFR1 expression in clinical specimens and PTC cells revealed that FGFR1 expression was enhanced in PTC. Using siRNA/shRNA silencing experiments, we found that FGFR1 downregulation impeded PTC cell growth, invasion, and migration and promoted apoptosis in vitro, as well as suppressed tumor growth in vivo. Bioinformatic analyses predicted the potential USP7-FGFR1 interplay and the potential binding between YY1 and the FGFR1 promoter. The mechanism study found that USP7 stabilized FGFR1 protein via deubiquitination, and YY1 could promote the transcription of FGFR1. Our rescue experiments showed that FGFR1 re-expression had a counteracting effect on USP7 downregulation-imposed in vitro alterations of cell functions and in vivo suppression of xenograft growth. In conclusion, our study identifies the deubiquitinating enzyme USP7 and the oncogenic transcription factor YY1 as potent inducers of FGFR1 overexpression. Designing inhibitors targeting FGFR1 or its upstream inducers USP7 and YY1 may be foreseen as a promising strategy to control PTC development.

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Ethics Approval

Xianning Central Hospital Institutional Ethics Committee approved the use of the human specimens (No. TDLL202209-06), This study was approved by the Xianning Central Hospital Animal Care and Use Committee (IACUC, No. ANHB202303-08)

How to Cite

Li, X. B., Li, J. L., Wang, C., Zhang, Y., & Li, J. (2024). Identification of mechanism of the oncogenic role of FGFR1 in papillary thyroid carcinoma. European Journal of Histochemistry, 68(3). https://doi.org/10.4081/ejh.2024.4048
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