USP7 promotes proliferation of papillary thyroid carcinoma cells through TBX3-mediated p57KIP2 repression
Abstract
Ubiquitin-specific protease 7 (USP7/HAUSP) is known to regulate multiple cellular phenomena, including cell cycle progression and proliferation, and is involved in binding and stabilizing specific target proteins through deubiquitylation. However, the detailed role of USP7 in papillary thyroid carcinoma (PTC) remains to be investigated. In this study, our results showed that USP7 was upregulated in PTC tissues compared with adjacent nontumour tissues. Consistently, a series of gain/loss functional assays in vivo and in vitro demonstrated the role of USP7 in promoting PTC cell proliferation. Furthermore, we showed that there was a negative correlation between USP7 and the CDK inhibitor p57 KIP2 expression in PTC tissues and that USP7 facilitated PTC cell proliferation by inhibiting p57 KIP2 . Mechanistically, USP7 inhibited p57 KIP2 expression by modulating TBX3, directly binding to TBX3, and decreasing its ubiquitination and degradation. Our findings demonstrated that USP7 played a critical oncogenic role in PTC tumorigenesis, suggesting that USP7 might act as a prognostic and therapeutic target for PTC progression.
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USP7 promotes PTC progression by directly binding and deubiquitylating TBX3 biochemically in vitro.
“Xie et al. reported that USP7 promoted PTC progression through directly binding and deubiquitylating TBX3 biochemically in vitro62.”
From Proteostatic reactivation of the developmental transcription factor TBX3 drives BRAF/MAPK-mediated tumorigenesis (2024) · cites this paper as [62]
Cites
The deubiquitinylation and localization of PTEN are regulated by a HAUSP-PML network
Song, M. S., Salmena, L., Carracedo, A., Egia, A., Lo-Coco, F., Teruya-Feldstein, J., & Pandolfi, P. P. (2008) · Nature · doi:10.1038/nature07290 · Cited by 548 · see citing works
Zhang, C., Lu, J., Zhang, Q.-W., Zhao, W., Guo, J.-H., Liu, S.-L., Wu, Y.-L., Jiang, B., & Gao, F.-H. (2016) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2016.08.025 · Cited by 67 · see citing works
Perkhofer, L., Walter, K., Costa, I. G., Carrasco, M. C. R., Eiseler, T., Hafner, S., Genze, F., Zenke, M., Bergmann, W., Illing, A., et al. (2016) · Stem Cell Research · doi:10.1016/j.scr.2016.08.007 · Cited by 39 · see citing works
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Zhang, Z., Wu, Y., Fu, J., Yu, X., Su, Y., Jia, S., Cheng, H., Shen, Y., He, X., Ren, K., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-48173-9 · Cited by 14 · see citing works
“Xie et al. reported that USP7 promoted PTC progression through directly binding and deubiquitylating TBX3 biochemically in vitro 62 .”
Background
- Authors
- Xie, P., Wang, H., Xie, J., Huang, Z., Chen, S., Cheng, X., Zhang, X., Liu, F., Li, Y., & Huang, D.
- Affiliations
- Nanchang University (CN)
- Shanghai Jiao Tong University (CN)
- Nanchang Normal University (CN)
- Corresponding author
- Li, Yun
- Huang, Da
- Venue
- Molecular and Cellular Endocrinology
- Publisher
- Elsevier BV
- Published
- 2020-12
- Volume
- 518
- Pages
- 111037
- ISSN
- 0303-7207 (ISSN-L)
- OpenAlex
- W3087091547
- Cited by
- 16
- References
- 3
- Citations by year
- 2025: 2 · 2024: 4 · 2023: 1 · 2022: 3 · 2021: 6
- FWCI
- 0.81
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular and Cellular Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81960521)
- Project of Educational Commission of Jiangxi Procince of China (170150)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Cancer Diagnosis and Treatment
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Keywords
- USP7, papillary thyroid carcinoma, TBX3, p57KIP2, deubiquitination, protein stability, cell proliferation, cyclin-dependent kinase inhibitors, oncogenes, carcinogenesis, prognostic targets
- MeSH terms
- Ubiquitin-Specific Peptidase 7, Thyroid Cancer, Papillary, Cells, Cultured, Humans, Thyroid Neoplasms, Signal Transduction, T-Box Domain Proteins, RNA Interference, Cell Proliferation, Cyclin-Dependent Kinase Inhibitor p57
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