https://doi.org/10.4081/ejh.2024.4048
Identification of mechanism of the oncogenic role of FGFR1 in papillary thyroid carcinoma
Submitted: 16 April 2024
Accepted: 3 July 2024
Published: 22 July 2024
Accepted: 3 July 2024
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All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
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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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