Preliminary Communication

Integrated analysis revealing the role of TET3-mediated MUC13 promoter hypomethylation in hepatocellular carcinogenesis

https://orcid.org/0000-0002-9784-8926

School of Life Sciences & Technology, Tongji University, Siping Road 1239, Shanghai, 200092, China

Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Sanmen Road 1279, Shanghai, 200434, China

‡These authors contributed equally to this work

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Hui Zhang‡

Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Sanmen Road 1279, Shanghai, 200434, China

‡These authors contributed equally to this work

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Yin Jia

Department of Laboratory & Diagnosis, Changhai Hospital, Navy Medical University, Changhai Road 168, Shanghai, 200433, China

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Qiuhong Man

*Author for correspondence: Tel.: +86 131 6150 8773;

E-mail Address: Manqiuhong307@163.com

Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Sanmen Road 1279, Shanghai, 200434, China

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Shanrong Liu

**Author for correspondence: Tel.: +86 180 1761 0468;

E-mail Address: liushanrong01@126.com

School of Life Sciences & Technology, Tongji University, Siping Road 1239, Shanghai, 200092, China

Department of Laboratory & Diagnosis, Changhai Hospital, Navy Medical University, Changhai Road 168, Shanghai, 200433, China

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Published Online:14 Mar 2023https://doi.org/10.2217/epi-2022-0395

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Abstract

Aim: To explore the function and underlying mechanism of MUC13 in hepatocellular carcinoma (HCC) oncogenesis. Materials & Methods: Online databases and software were used to perform analyses of expression, methylation and enrichment pathway. Experiments were performed to confirm the results using HCC cells in vitro. Results: MUC13 was upregulated in HCC and liver cancer stem cells (CSCs) and had a positive influence on CSC generation. Further analyses revealed that MUC13 with promoter hypomethylated was regulated by DNA demethylase TET3, which was overexpressed in HCC and liver CSCs. Conclusion: These results strongly suggested that high TET3 expression in liver CSCs may mediate MUC13 upregulation via promoter hypomethylation and thereby contribute to hepatocellular carcinogenesis.

Plain language summary

To understand the function and mechanism of MUC13 in hepatocellular carcinogenesis, online databases and software were used to analyze MUC13 expression, promoter methylation and enrichment pathway. Experiments were also performed to further confirm the results in vitro. MUC13 was upregulated in hepatocellular carcinoma (HCC) and had a positive influence on cancer stem cell (CSC) generation. Further analyses revealed that MUC13 with promoter hypomethylated was regulated by DNA demethylase TET3, which was overexpressed in HCC and liver CSCs. Importantly, it was revealed that MUC13 with promoter hypomethylated, was regulated by TET3, which was overexpressed in HCC and liver CSCs. These results strongly suggest that high TET3 expression in liver CSCs may mediate promoter hypomethylation and expression upregulation of MUC13, thereby contributing to hepatocellular carcinogenesis.

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Papers of special note have been highlighted as: • of interest; •• of considerable interest

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Vol. 14, No. 24

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History

Received 6 November 2022

Accepted 28 February 2023

Published online 14 March 2023

Published in print December 2022

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Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.futuremedicine.com/doi/suppl/10.2217/epi-2022-0395

Financial & competing interests disclosure

This work was supported by the State Key Program of National Natural Science Foundation of China (no. 81730076) and the Health and Family Planning Commission of Hongkou District, Shanghai (no. 2002-09). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

This study was approved by the Institutional Ethics Committee of Medicine of the Navy Medical University. Informed consent was obtained from all patients.

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