Transcription factor E2F3 activates CDC25B to regulate DNA damage and promote mitoxantrone resistance in stomach adenocarcinoma

• Published in: Molecular biology reports 2024-12, Vol.51 (1), p.90-90, Article 90
• Main Authors: Pan, Xiaoming, Xu, Chaobo, Cheng, Guoxiong, Chen, Zhengwei, Liu, Ming, Mei, Yijun
• Format: Article
• Language: English
• Subjects: Adenocarcinoma; Animal Anatomy; Animal Biochemistry; Bioinformatics; Biomedical and Life Sciences; Cancer; Cdc25B phosphatase; Cell cycle; Cell viability; Comet assay; Cytoplasm; DNA damage; Gastric cancer; Histology; Life Sciences; Mismatch repair; Mitosis; Mitoxantrone; Morphology; Nucleotide excision repair; Original Article; Therapeutic targets; Transcription factors; Tumors
• ISSN: 0301-4851; 1573-4978
• DOI: 10.1007/s11033-023-08933-0

Background CDC25B, as a member of the cell cycle regulating protein family, is located in the cytoplasm and is involved in the transition of the cell cycle and mitosis. CDC25B is highly expressed in various tumors and is a newly discovered oncogene. This study aimed to investigate the impact of CDC25B on mitoxantrone resistance in stomach adenocarcinoma (STAD) and its possible mechanisms. Methods This study analyzed the expression of CDC25B and its potential transcription factor E2F3 in STAD, as well as the IC 50 values of tumor tissues by bioinformatics analysis. Expression levels of CDC25B and E2F3 in STAD cells were measured by qRT-PCR. MTT was utilized to evaluate cell viability and IC 50 values of STAD cells, and comet assay was utilized to analyze the level of DNA damage in STAD cells. Western blot was used to analyze the expression of DNA damage-related proteins. The targeting relationship between E2F3 and CDC25B was validated by dual-luciferase and ChIP assays. Results Bioinformatics analysis and molecular experiments showed that CDC25B and E2F3 were highly expressed in STAD, and CDC25B was enriched in the mismatch repair and nucleotide excision repair pathways. The IC 50 values of tumor tissues with high expression of CDC25B were relatively high. Dual-luciferase and ChIP assays confirmed that CDC25B could be transcriptionally activated by E2F3. Cell experiments revealed that CDC25B promoted mitoxantrone resistance in STAD cells by regulating DNA damage. Further research found that low expression of E2F3 inhibited mitoxantrone resistance in STAD cells by DNA damage, but overexpression of CDC25B reversed the impact of E2F3 knockdown on mitoxantrone resistance in STAD cells. Conclusion This study confirmed a novel mechanism by which E2F3/CDC25B mediated DNA damage to promote mitoxantrone resistance in STAD cells, providing a new therapeutic target for STAD treatment.