DNMT3b promotes proliferation and invasion by mediating HOPX DNA methylation in lung cancer

DNMT3B is an important DNA methyltransferase related with unfavorable outcomes for cancer patients. DNMT3B can promote the progression of multifarious malignant tumors. Nevertheless, the functional mechanisms through which DNMT3B promotes the malignant progression of lung cancer remain incompletely understood and require further investigation. In this study, we demonstrated that DNMT3B promoted proliferation, migration, and invasion of lung cancer cells <i>in vitro</i> and facilitated tumor growth <i>in vivo</i> in xenograft models. Mechanistically, DNMT3B could downregulate HOPX expression through DNA methylation. Consistently, the DNMT inhibitor (SGI-1027) could significantly upregulate HOPX expression level. High HOPX expression effectively suppressed the proliferation, migration, and invasion of lung cancer cells. In contrast, HOPX knockdown partially recovered the malignant phenotypes of lung cancer cells treated with SGI-1027 or si-DNMT3B. In conclusion, these findings provide a rationale for targeting DNMT3B-mediated HOPX DNA methylation and identify crucial molecular targets for lung cancer therapy.

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Journal
iScience
Published
2025-12-05
DOI
https://doi.org/10.1016/j.isci.2025.114347
Primary Topic
Epigenetics and DNA Methylation
Type
article
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0.00
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article

DNMT3b promotes proliferation and invasion by mediating HOPX DNA methylation in lung cancer

Guizhen Zhang, Songfeng Zhao, Dongdong Song, Yun Wang et al.
iScience
Epigenetics and DNA Methylation
article

DNMT3b promotes proliferation and invasion by mediating HOPX DNA methylation in lung cancer

Guizhen Zhang, Songfeng Zhao, Dongdong Song, Yun Wang, Kelei Guan, Yanxia Ding
article en

Abstract

DNMT3B is an important DNA methyltransferase related with unfavorable outcomes for cancer patients. DNMT3B can promote the progression of multifarious malignant tumors. Nevertheless, the functional mechanisms through which DNMT3B promotes the malignant progression of lung cancer remain incompletely understood and require further investigation. In this study, we demonstrated that DNMT3B promoted proliferation, migration, and invasion of lung cancer cells <i>in vitro</i> and facilitated tumor growth <i>in vivo</i> in xenograft models. Mechanistically, DNMT3B could downregulate HOPX expression through DNA methylation. Consistently, the DNMT inhibitor (SGI-1027) could significantly upregulate HOPX expression level. High HOPX expression effectively suppressed the proliferation, migration, and invasion of lung cancer cells. In contrast, HOPX knockdown partially recovered the malignant phenotypes of lung cancer cells treated with SGI-1027 or si-DNMT3B. In conclusion, these findings provide a rationale for targeting DNMT3B-mediated HOPX DNA methylation and identify crucial molecular targets for lung cancer therapy.

iScienceVol. 29(2)
First Affiliated Hospital of Zhengzhou University (CN)
Openalex Percentile: Top 65%
Epigenetics and DNA Methylation
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DNMT3b promotes proliferation and invasion by mediating HOPX DNA methylation in lung cancer — Guizhen Zhang, Songfeng Zhao, et al. · iScience (2025) | TGRS Research Map | TGRS