Evidence map›Paper›PMID 39680331›Full record

ArticleBiochemical genetics2025

METTL3-Mediated m6A Methylation of USP21 Contributes to Hepatocellular Carcinoma Progression by Stabilizing H2BFS Through Deubiquitination.

Peng Yao, Xiaozheng Li, Jiasui Chai, Jiejie Dong, Yan Chen, Tong Zhang, Xingren Guo

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Article in Biochemical genetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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5 · Who and what money

Authors and funding

7 authors.

Peng YaoDepartment of Hepatobiliary Surgery, Yuncheng Central Hospital, The Eighth Clinical College of Shanxi Medical University, No. 3690, Hedong Street, Yuncheng, 044031, Shanxi, China. yaopengyc@163.com.
Xiaozheng LiDepartment of Hepatobiliary Surgery, Yuncheng Central Hospital, The Eighth Clinical College of Shanxi Medical University, No. 3690, Hedong Street, Yuncheng, 044031, Shanxi, China.
Jiasui ChaiDepartment of Hepatobiliary Surgery, Yuncheng Central Hospital, The Eighth Clinical College of Shanxi Medical University, No. 3690, Hedong Street, Yuncheng, 044031, Shanxi, China.
Jiejie DongDepartment of Hepatobiliary Surgery, Yuncheng Central Hospital, The Eighth Clinical College of Shanxi Medical University, No. 3690, Hedong Street, Yuncheng, 044031, Shanxi, China.
Yan ChenDepartment of Hepatobiliary Surgery, Yuncheng Central Hospital, The Eighth Clinical College of Shanxi Medical University, No. 3690, Hedong Street, Yuncheng, 044031, Shanxi, China.
Tong ZhangDepartment of Hepatobiliary Surgery, Yuncheng Central Hospital, The Eighth Clinical College of Shanxi Medical University, No. 3690, Hedong Street, Yuncheng, 044031, Shanxi, China.
Xingren GuoDepartment of Hepatobiliary Surgery, Yuncheng Central Hospital, The Eighth Clinical College of Shanxi Medical University, No. 3690, Hedong Street, Yuncheng, 044031, Shanxi, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Deubiquitinases play essential roles in hepatocellular carcinoma (HCC) progression, however, the role of ubiquitin-specific peptidase 21 (USP21) in HCC development remains unclear. The present work aims to analyze the effect of USP21 on tumor property of HCC cells and the underlying mechanism. mRNA expression levels of USP21 and H2BFS were analyzed by quantitative real-time polymerase chain reaction. Protein expression of USP21, E-cadherin, N-cadherin, Vimentin, H2BFS and methyltransferase 3 (METTL3) was assessed by western blotting assay or immunohistochemistry assay. Clonogenicity assay was used to analyze cell proliferation. Flow cytometry assay was performed to quantify apoptotic rate of cells. Wound-healing assay and transwell assay were conducted to analyze cell migration and invasion, respectively. Xenograft mouse model assay was performed to determine the effect of USP21 knockdown on tumor formation. m6A RNA immunoprecipitation assay (MeRIP) was used to analyze the effect of METTL3 silencing on methylated level of USP21. USP21 expression was upregulated in HCC tissues and cells when compared with control groups. USP21 silencing inhibited proliferation, migration and invasion and induced apoptosis of HCC cells, accompanied by the increased E-cadherin protein expression and decreased N-cadherin and Vimentin protein expression. Moreover, USP21 knockdown delayed tumor formation in vivo. USP21 stabilized H2BFS by deubiquitination, and H2BFS overexpression attenuated USP21 silencing-induced effects in HCC cells. Further, METTL3-mediated m6A methylation of USP21. METTL3-mediated m6A methylation of USP21 promoted HCC progression by stabilizing H2BFS through deubiquitination.

Indexed as

Carcinoma, HepatocellularLiver NeoplasmsMethyltransferasesUbiquitin ThiolesteraseAnimalsCadherinsCell Line, TumorCell MovementCell ProliferationDisease ProgressionGene Expression Regulation, NeoplasticHumansMaleMethylationMiceMice, NudeCadherinsMethyltransferasesMETTL3 protein, humanUbiquitin ThiolesteraseUSP21 protein, humanH2BFSHCCMETTL3USP21

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.