Flap endonuclease 1 Facilitated Hepatocellular Carcinoma Progression by Enhancing USP7/MDM2-mediated P53 Inactivation

Bian, Saiyan; Ni, Wenkai; Zhu, Mengqi; Zhang, Xue; Qiang, Yuwei; Zhang, Jianping; Ni, Zhiyu; Shen, Yiping; Qiu, Shi; Song, Qianqian; Xiao, Mingbing; Zheng, Wenjie

doi:10.7150/ijbs.68179

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Int J Biol Sci 2022; 18(3):1022-1038. doi:10.7150/ijbs.68179 This issue Cite

Research Paper

Flap endonuclease 1 Facilitated Hepatocellular Carcinoma Progression by Enhancing USP7/MDM2-mediated P53 Inactivation

Saiyan Bian^1#, Wenkai Ni^1#, Mengqi Zhu^1,2,3#, Xue Zhang^1,2,3, Yuwei Qiang^1,2, Jianping Zhang^1,2, Zhiyu Ni^1,2, Yiping Shen^1,2, Shi Qiu^1,2, Qianqian Song⁴, Mingbing Xiao^1✉, Wenjie Zheng^1,3✉

1. Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong 226001, P.R. China.
2. School of Medicine, Nantong University, Nantong 226001, P.R. China.
3. Department of Oncology, Affiliated Hospital of Nantong University, Nantong 226001, P.R. China.
4. Department of Radiology, Wake Forest School of Medicine, Winston-Salem 27157, USA.
# Saiyan Bian, Wenkai Ni, and Mengqi Zhu contributed equally to this study.

Citation:

Bian S, Ni W, Zhu M, Zhang X, Qiang Y, Zhang J, Ni Z, Shen Y, Qiu S, Song Q, Xiao M, Zheng W. Flap endonuclease 1 Facilitated Hepatocellular Carcinoma Progression by Enhancing USP7/MDM2-mediated P53 Inactivation. Int J Biol Sci 2022; 18(3):1022-1038. doi:10.7150/ijbs.68179. https://www.ijbs.com/v18p1022.htm

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Abstract

Overexpression of Flap endonuclease 1 (FEN1) has been previously implicated in hepatocellular carcinoma (HCC), while its expression features and mechanisms remain unclear. In the current study, differential expression genes (DEGs) were screened in HCC tissues and normal liver tissues in 4 Gene Expression Omnibus (GEO) datasets. FEN1, one of the hub co-overexpressed genes, was further determined overexpressed in HCC tissues in TCGA, local HCC cohorts, and hepatocarcinogenesis model. In addition, high expression of FEN1 indicated poor prognosis of HCC patients. Loss-of-function and gain-of-function assays demonstrated that FEN1 enhanced the proliferation, cell cycle phage transition, migration/ invasion, therapy resistance, xenograft growth, and epithelial-mesenchymal transition (EMT) process of HCC cells. Mechanically, FEN1 could inactivate P53 signaling by preventing the ubiquitination and degradation of mouse double minute 2 (MDM2) via recruiting ubiquitin-specific protease 7 (USP7). Interfering USP7 with P22077 significantly reversed the malignant phenotypes activated by FEN1. In conclusion, this study suggests FEN1 as a robust prognostic biomarker and potential target for HCC.

Keywords: Flap endonuclease 1, hepatocellular carcinoma, P53, mouse double minute 2, ubiquitin-specific protease 7, molecular target

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APA

Bian, S., Ni, W., Zhu, M., Zhang, X., Qiang, Y., Zhang, J., Ni, Z., Shen, Y., Qiu, S., Song, Q., Xiao, M., Zheng, W. (2022). Flap endonuclease 1 Facilitated Hepatocellular Carcinoma Progression by Enhancing USP7/MDM2-mediated P53 Inactivation. International Journal of Biological Sciences, 18(3), 1022-1038. https://doi.org/10.7150/ijbs.68179.

ACS

Bian, S.; Ni, W.; Zhu, M.; Zhang, X.; Qiang, Y.; Zhang, J.; Ni, Z.; Shen, Y.; Qiu, S.; Song, Q.; Xiao, M.; Zheng, W. Flap endonuclease 1 Facilitated Hepatocellular Carcinoma Progression by Enhancing USP7/MDM2-mediated P53 Inactivation. Int. J. Biol. Sci. 2022, 18 (3), 1022-1038. DOI: 10.7150/ijbs.68179.

NLM

CSE

Bian S, Ni W, Zhu M, Zhang X, Qiang Y, Zhang J, Ni Z, Shen Y, Qiu S, Song Q, Xiao M, Zheng W. 2022. Flap endonuclease 1 Facilitated Hepatocellular Carcinoma Progression by Enhancing USP7/MDM2-mediated P53 Inactivation. Int J Biol Sci. 18(3):1022-1038.

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