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

**Authors:** Kelei Guan, Songfeng Zhao, Guizhen Zhang, Yun Wang, Dongdong Song, Yanxia Ding

PMC · DOI: 10.1016/j.isci.2025.114347 · iScience · 2025-12-05

## TL;DR

This study shows that DNMT3B promotes lung cancer growth by silencing HOPX through DNA methylation, suggesting a new therapeutic target.

## Contribution

The study identifies DNMT3B-mediated HOPX DNA methylation as a novel mechanism promoting lung cancer progression.

## Key findings

- DNMT3B promotes proliferation, migration, and invasion of lung cancer cells.
- DNMT3B downregulates HOPX expression through DNA methylation.
- High HOPX expression suppresses lung cancer cell proliferation and invasion.

## 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 in vitro and facilitated tumor growth in vivo 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.

•DNMT3B promotes proliferation, migration, and invasion of lung cancer cells•DNMT3B downregulates HOPX expression through DNA methylation•DNMT3B-mediated HOPX silencing provides a promising therapeutic target for lung cancer

DNMT3B promotes proliferation, migration, and invasion of lung cancer cells

DNMT3B downregulates HOPX expression through DNA methylation

DNMT3B-mediated HOPX silencing provides a promising therapeutic target for lung cancer

Biological sciences; Epigenetics; Cell biology; Cancer

## Linked entities

- **Genes:** DNMT3B (DNA methyltransferase 3 beta) [NCBI Gene 1789], HOPX (HOP homeobox) [NCBI Gene 84525]
- **Chemicals:** SGI-1027 (PubChem CID 24858111)
- **Diseases:** lung cancer (MONDO:0005138)

## Full-text entities

- **Genes:** HOPX (HOP homeobox) [NCBI Gene 84525] {aka CAMEO, HOD, HOP, LAGY, NECC1, OB1}, DNMT3B (DNA methyltransferase 3 beta) [NCBI Gene 1789] {aka FSHD4, ICF, ICF1, M.HsaIIIB}, DNMT1 (DNA methyltransferase 1) [NCBI Gene 1786] {aka ADCADN, AIM, CXXC9, DNMT, HSN1E, MCMT}
- **Diseases:** lung cancer (MESH:D008175), cancer (MESH:D009369)
- **Chemicals:** SGI-1027 (MESH:C581203)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

11 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12876300/full.md

## References

42 references — full list in the complete paper: https://tomesphere.com/paper/PMC12876300/full.md

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Source: https://tomesphere.com/paper/PMC12876300