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Epigenetic inhibition of lncRNA GMDS-AS1 by methyltransferase ESET promoted cell viability and metastasis of hepatocellular carcinoma

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Abstract

Background

Long noncoding RNA (lncRNAs) GMDS-AS1 has been reported as a tumor regulator in tumor growth and metastasis, but its effect in hepatocellular carcinoma (HCC) remains unclear. ESET, a histone H3K9 methyl-transferase, is involved in epigenomic regulation of tumor progression in multiple cancers. However, the correlation between ESET and lncRNA in HCC is less reported.

Methods

Quantitative real-time PCR (qRT-PCR) was taken to determine the expression of ESET and GMDS-AS1. Western blot was taken to determine the target protein levels of ESET and GMDS-AS1. Online database and bioinformatics analysis were used to screen abnormally expressed genes. Luciferase assay was performed to confirm the binding of GMDS-AS1 and PSMB1. Ki67 and Edu were used for evaluated the proliferation of tumor cells. ChIP assay was performed to verify the relationship between H3K9me1 and lncRNA GMDS-AS1 promoter. Transwell was taken to determine the migration and invasion ability of tumor cells. CCK-8 was used for determining the viability of tumor cells. Flow cytometry was performed to detect the cell cycle of tumor cells.

Results

The expression of GMDS-AS1 was decreased and the expression of ESET was increased in HCC. GMDS-AS1 inhibition contributed to tumor development, and this effect was closely related to epigenetic inhibition of GMDS-AS1 by ESET. PSMB1, a downstream target of GMDS-AS1, promoted the tumor proliferation and was negatively regulated by GMDS-AS1.

Conclusion

Our result demonstrates anti-tumorigenic traits of lncRNA GMDS-AS1 in HCC and explains its pattern of regulation mediated by ESET. Our work unmasked an essential role of GMDS-AS1 in HCC progression and detected a novel pathway for ESET to promote HCC.

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Data availability

The sequencing data used in Fig. 4A, B were download from the GEO data base [https://www.ncbi.nlm.nih.gov/geo/, GSE138178]. The other data are available in the method of this article.

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Acknowledgements

We greatly appreciate the support from the Guangxi University young and middle-aged teachers research ability enhancement project (KY2016LX257), Guangxi University Key Laboratory Project (kfkt2016009) and High-level talents research project of the Affiliated Hospital of Youjiang Medical University for Nationalities (Y20196303).

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Authors and Affiliations

  1. The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, 533000, Guang Xi, China

    Junling Huang & Guangzhi Li

  2. People’s Hospital of Baise, Baise, 533000, Guang Xi, China

    Tengmeng Zhong

  3. Youjiang Medical University for Nationalities, Baise, 533000, Guang Xi, China

    Shuzhen Wang & Rujuan Qin

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Contributions

JH: Conceptualization, Writing—Original Draft, Writing–Editing; TZ: Validation, Supervision, Funding acquisition, Project administration; GL: Methodology, Investigation, Resources, Experimentation; SW: Experimentation; RQ: Formal analysis, Data Curation, Visualization.

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Correspondence to Tengmeng Zhong.

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This study was approved by the Ethics Committee of the Affiliated Hospital of Youjiang Medical University for Nationalities. The study was conducted in accordance with the Declaration of Helsinki.

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All authors have read and approved the final manuscript.

Human participants and/or animals and Informed consent

This study involves animal experiments were approved by the Ethics Committee of the Affiliated Hospital of Youjiang Medical University for Nationalities. This study does not involve human participants.

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Huang, J., Zhong, T., Li, G. et al. Epigenetic inhibition of lncRNA GMDS-AS1 by methyltransferase ESET promoted cell viability and metastasis of hepatocellular carcinoma. Clin Transl Oncol 25, 1793–1804 (2023). https://doi.org/10.1007/s12094-023-03077-w

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