DNA Hypermethylation of the ZNF382 Promoter Region and Low mRNA Expression of ZNF382 Promote Diffuse Large B‐Cell Lymphoma Occurrence and Progression

Journal article

Background: The pathogenesis of diffuse large B‐cell lymphoma (DLBCL) remains unclear. Zinc finger protein 382 (ZNF382) expression is significantly downregulated in DLBCL, which is associated with poor prognosis. However, the underlying mechanisms remain unknown. Aims: To investigate the association between DNA methylation of the promoter region of ZNF382 and ZNF382 expression with the occurrence and progression of DLBCL and to analyze the clinical significance of ZNF382 in DLBCL. Methods and Results: DLBCL cell lines and reactive hyperplastic lymph node tissues were used as the experimental subjects. Methylation‐specific polymerase chain reaction and reverse‐transcription polymerase chain reaction analyses revealed significantly higher methylation of the promoter region of ZNF382 (p < 0.0001), whereas ZNF382 mRNA expression was significantly lower (p < 0.01) in DLBCL cells compared with those in reactive hyperplastic lymph node tissues. Cells were treated with the demethylating agent decitabine (DAC), and the methylation status of the promoter and expression levels of ZNF382 were determined. ZNF382 promoter methylation was significantly reduced (p < 0.01) in DLBCL cells, whereas ZNF382 mRNA expression was significantly increased (p < 0.01) compared with those in the control cells. Furthermore, compared with that in the blank control group, the apoptosis rate of DLBCL cells was significantly increased following DAC intervention (p < 0.01). A cell model of ZNF382 overexpression was constructed, and its proliferation, migration, and clonogenic capacities were detected using CCK‐8, Transwell, and soft agar assays, respectively. Compared with those of the vector control group, the cell proliferation, migration, and clone formation abilities of the ZNF382 overexpression group were significantly inhibited (p < 0.01). Conclusion: DNA hypermethylation in the promoter region of ZNF382 and low ZNF382 mRNA expression are closely related to the occurrence and progression of DLBCL. Moreover, ZNF382 overexpression significantly increased apoptosis and inhibited cell proliferation, migration, and clone formation. Therefore, ZNF382 has potential as a therapeutic target in the treatment of DLBCL.

Authors: An, W; Guo, S; Liu, S; Xiao, P; Mi, E

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Wiley
• Journal: Cancer Reports
• Volume: 9
• Issue: 2
• Article number: e70502
• Publication date: 2026-02-19
• Acceptance date: 2026-02-03
• DOI: 10.1002/cnr2.70502
• EISSN: 2573-8348
• ISSN: 2573-8348
• Language: English
• Keywords: decitabine; ZNF382; diffuse large B‐cell lymphoma; methylation