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.

中文翻译：

---

RAD51 是胰腺癌预后的潜在标志物并调节细胞增殖。

背景 DNA 损伤和修复途径被认为是制定抗癌策略的一个有前景的目标。RAD51，也称为 RECA，是一种重组酶，在同源重组中执行关键步骤。RAD51由于其在肿瘤进展中的功能以及在肿瘤对化疗的耐药性中的决定性作用，最近受到了相当多的关注。然而，其在胰腺癌中的作用却很少被研究。在本报告中，我们提供了证据表明 RAD51 受 KRAS 调节，可促进胰腺癌细胞增殖。此外，RAD51 通过靶向缺氧诱导因子 1α (HIF1α) 来调节有氧糖酵解。方法使用TCGA（癌症基因组图谱）数据集分析来检查RAD51表达对胰腺癌患者总体生存的影响。慢病毒介导的转导用于沉默 RAD51 和 KRAS 表达。实时定量PCR和蛋白质印迹分析验证了敲低效应的功效。还对胰腺癌细胞中的糖酵解过程进行了分析。使用CCK-8（细胞计数试剂盒-8）增殖测定法测定细胞增殖。结果 RAD51 水平较高的胰腺癌患者生存率较差。在胰腺癌细胞中，RAD51 正向调节细胞增殖、减少细胞内活性氧 (ROS) 的产生并增加 HIF1α 蛋白水平。KRAS/MEK/ERK 激活增加了 RAD51 表达。此外，RAD51 是有氧糖酵解的正调节剂。结论 本研究揭示了 RAD51 在胰腺癌中的新作用，其与总体生存预测相关，可能通过涉及有氧糖酵解调节的机制来实现。这些发现可能为胰腺癌提供新的预测和治疗靶点。