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RAD51 is a potential marker for prognosis and regulates cell proliferation in pancreatic cancer
Xiaomeng Zhang1,2, Ningyi Ma3,4, Weiqiang Yao1,2
11Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, 200032 China.
Background:
The DNA damage and repair pathway is considered a promising target for developing strategies against cancer. RAD51, also known as RECA, is a recombinase that performs the critical step in homologous recombination. RAD51 has recently received considerable attention due to its function in tumor progression and its decisive role in tumor resistance to chemotherapy. However, its role in pancreatic cancer has seldom been investigated. In this report, we provide evidence that RAD51, regulated by KRAS, promotes pancreatic cancer cell proliferation. Furthermore, RAD51 regulated aerobic glycolysis by targeting hypoxia inducible factor 1α (HIF1α).
Methods:
TCGA (The Cancer Genome Atlas) dataset analysis was used to examine the impact of RAD51 expression on overall survival of pancreatic cancer patients. Lentivirus-mediated transduction was used to silence RAD51 and KRAS expression. Quantitative real-time PCR and western blot analysis validated the efficacy of the knockdown effect. Analysis of the glycolysis process in pancreatic cancer cells was also performed. Cell proliferation was determined using a CCK-8 (Cell Counting Kit-8) proliferation assay.
Results:
Pancreatic cancer patients with higher levels of RAD51 exhibited worse survival. In pancreatic cancer cells, RAD51 positively regulated cell proliferation, decreased intracellular reactive oxygen species (ROS) production and increased the HIF1α protein level. KRAS/MEK/ERK activation increased RAD51 expression. In addition, RAD51 was a positive regulator of aerobic glycolysis.
Conclusion:
The present study reveals novel roles for RAD51 in pancreatic cancer that are associated with overall survival prediction, possibly through a mechanism involving regulation of aerobic glycolysis. These findings may provide new predictive and treatment targets for pancreatic cancer.
Insights
RAD51 promotes pancreatic cancer cell proliferation and aerobic glycolysis by regulating HIF1α. Higher RAD51 levels correlate with worse patient survival, indicating its potential as a predictive and therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- DNA damage and repair pathways are key targets in cancer therapy.
- RAD51 (RECA) is crucial for homologous recombination and implicated in tumor progression and chemoresistance.
- The role of RAD51 in pancreatic cancer remains under-investigated.
Purpose of the Study:
- To investigate the role of RAD51 in pancreatic cancer progression.
- To explore the relationship between RAD51, KRAS, and aerobic glycolysis in pancreatic cancer.
- To assess RAD51 as a prognostic marker for pancreatic cancer survival.
Main Methods:
- Analysis of The Cancer Genome Atlas (TCGA) dataset for RAD51 expression and patient survival.
- Lentivirus-mediated knockdown of RAD51 and KRAS in pancreatic cancer cells.
- Quantitative real-time PCR and western blot to confirm knockdown efficacy.
- Assays to evaluate cell proliferation and aerobic glycolysis, including HIF1α levels.
Main Results:
- Elevated RAD51 expression is linked to poorer overall survival in pancreatic cancer patients.
- RAD51 knockdown reduced pancreatic cancer cell proliferation and ROS production.
- KRAS/MEK/ERK pathway activation positively regulates RAD51 expression.
- RAD51 was identified as a key regulator of aerobic glycolysis via HIF1α.
Conclusions:
- RAD51 plays a significant role in pancreatic cancer, influencing proliferation and aerobic glycolysis.
- RAD51 may serve as a predictive biomarker for patient outcomes in pancreatic cancer.
- Targeting RAD51 presents a potential therapeutic strategy for pancreatic cancer.
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