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Updated: Jul 15, 2025

Author Spotlight: Unveiling Transmembrane Protein Family-Related Markers in Gastric Cancer and Implications for Targeted Therapies
Published on: September 15, 2023
E2F3/CDCA2 reduces radiosensitivity in gastric adenocarcinoma by activating PI3K/AKT pathway
Jun Gao1, Huaqiao Wang1, Xiujuan Qiu2
1Department of General Surgery, Xiangyang No.1 People's Hospital, Hubei University of Medicine, Xiangyang, China.
Objectives:
Gastric adenocarcinoma is primarily responsible for tumor-associated deaths and its incidence is increasing global. CDCA2 is a nuclear protein binding to protein phosphatase one γ (PP1γ) and plays a pro-oncogenic role in tumors. This study aimed to elucidate the biological function of CDCA2 in gastric adenocarcinoma progression and radiosensitivity, as well as its potential mechanisms.
Methods:
Differentially expressed mRNAs in gastric adenocarcinoma were obtained by bioinformatics and upstream regulatory factors were predicted. The correlation between their expressions was analyzed. The expressions of E2F3 and CDCA2 in cells were assayed by qRT-PCR and their regulatory relationship was validated by molecular experiments. Cell viability was tested via CCK-8. Cell proliferation and survival after radiotherapy were determined by colony formation assay. The expressions of PI3K/AKT pathway-related proteins were assessed through western blot.
Results:
CDCA2 was significantly upregulated in gastric adenocarcinoma tissues and cells, promoted cell proliferation, and reduced radiosensitivity. The impact of CDCA2 on cell proliferation and radiosensitivity was reversed by the PI3K/AKT inhibitor. Furthermore, the upstream transcription factor of CDCA2 was found to be E2F3, which was highly expressed in gastric adenocarcinoma. The binding relationship between the two was validated by dual luciferase and ChIP experiments. The rescue experiment showed that E2F3 activated CDCA2 to drive cell proliferation and reduce radiosensitivity through PI3K/AKT pathway in gastric adenocarcinoma.
Conclusion:
In summary, this study found that E2F3 activated CDCA2 to drive cell proliferation and reduce radiosensitivity in gastric adenocarcinoma through the PI3K/AKT pathway, suggesting that E2F3/CDCA2 axis is a new therapeutic target for gastric adenocarcinoma.
Advances In Knowledge:
1. CDCA2 reduced the radiosensitivity of gastric adenocarcinoma cells;2. CDCA2 reduced the radiosensitivity of gastric adenocarcinoma cells through the PI3K/AKT pathway;3. E2F3 activated CDCA2 to reduce the radiosensitivity of gastric adenocarcinoma cells through the PI3K/AKT pathway.
Insights
The E2F3/CDCA2 axis promotes gastric adenocarcinoma progression and reduces radiosensitivity by activating the PI3K/AKT pathway. This axis represents a potential new therapeutic target for this increasing global cancer.
Area of Science:
- Oncology
- Molecular Biology
Background:
- Gastric adenocarcinoma is a leading cause of cancer deaths with rising incidence.
- CDCA2, a nuclear protein, is implicated in promoting tumor growth.
Purpose of the Study:
- To investigate the role of CDCA2 in gastric adenocarcinoma progression and radiosensitivity.
- To elucidate the underlying molecular mechanisms involving CDCA2.
Main Methods:
- Bioinformatic analysis to identify differentially expressed genes and upstream regulators.
- Quantitative real-time PCR (qRT-PCR) and molecular experiments to validate regulatory relationships.
- Cell viability (CCK-8), proliferation, and radiosensitivity assays (colony formation), and Western blot analysis of the PI3K/AKT pathway.
Main Results:
- CDCA2 was significantly upregulated in gastric adenocarcinoma, promoting proliferation and decreasing radiosensitivity.
- The PI3K/AKT pathway inhibitor reversed the effects of CDCA2 on proliferation and radiosensitivity.
- E2F3 was identified as an upstream transcription factor that activates CDCA2, driving proliferation and reducing radiosensitivity via the PI3K/AKT pathway.
Conclusions:
- The E2F3/CDCA2 axis promotes gastric adenocarcinoma cell proliferation and reduces radiosensitivity.
- This axis operates through the activation of the PI3K/AKT pathway.
- The E2F3/CDCA2 axis presents a novel therapeutic target for gastric adenocarcinoma.
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