基因RAD51AP1,也称为RAD51相关蛋白1,是一种编码蛋白质的基因,在许多癌症中发挥着重要作用。RAD51AP1与RAD51蛋白相互作用,参与同源重组(HR),这是一种关键的DNA损伤修复途径。HR在保持基因组完整性和防止癌症发生中起着至关重要的作用。RAD51AP1的表达在多种癌症中上调,包括胰腺癌、肝细胞癌、卵巢癌和子宫内膜癌,并且与不良预后相关。
在胰腺癌中,RAD51AP1通过PI3K/AKT/NF-κB信号通路促进癌细胞的增殖、迁移和侵袭[1]。抑制RAD51AP1的表达可以显著降低这些细胞的功能,并抑制肿瘤生长。此外,RAD51AP1在转录活跃区域与DNA双链断裂(DSB)相互作用,形成DNA-RNA杂交体,从而促进HR[2]。
在HBV相关肝细胞癌(HCC)中,RAD51AP1是促进癌细胞增殖和转移的关键基因[3]。HBV感染可以增强LINC01419/miR-8070/RAD51AP1轴,从而促进癌细胞的增殖和转移。此外,RAD51AP1还可以通过Wnt/β-catenin信号通路促进HCC的发生和发展。
在卵巢癌中,RAD51AP1在基因和蛋白质水平上均过表达,并且与不良预后相关[4]。RAD51AP1的表达与肿瘤的分级、复发和淋巴结转移相关。此外,RAD51AP1还可以通过TGF-β/Smad信号通路促进卵巢癌的进展[5]。
在子宫内膜癌中,E2F7转录因子可以激活RAD51AP1的表达,并通过脂肪酸代谢途径抑制子宫内膜癌细胞对5-FU化疗的敏感性[6]。
在肝细胞癌中,RAD51AP1是免疫相关的预后生物标志物和治疗反应预测因子。RAD51AP1的表达与不良预后相关,并且与免疫抑制微环境相关。此外,RAD51AP1的表达还与对Bexarotene、Doxorubicin、Gemcitabine和Tipifarnib等药物的敏感性相关[7]。
综上所述,RAD51AP1是一种重要的基因,在多种癌症中发挥着重要作用。RAD51AP1参与HR和DNA损伤修复,并且在肿瘤生长、转移和化疗敏感性中发挥着关键作用。因此,RAD51AP1可能是癌症治疗和预防的潜在靶点[1,3,4,5,6,7]。
参考文献:
1. Wang, Yongkun, Li, Yingchun, Ran, Cui, Chen, Bo, Jiang, Xiaohua. 2023. The gene RAD51AP1 promotes the progression of pancreatic cancer via the PI3K/Akt/NF-κB signaling pathway. In Neoplasma, 70, 722-732. doi:10.4149/neo_2023_230614N310. https://pubmed.ncbi.nlm.nih.gov/37962862/
2. Ouyang, Jian, Yadav, Tribhuwan, Zhang, Jia-Min, Lan, Li, Zou, Lee. 2021. RNA transcripts stimulate homologous recombination by forming DR-loops. In Nature, 594, 283-288. doi:10.1038/s41586-021-03538-8. https://pubmed.ncbi.nlm.nih.gov/33981036/
3. Wan, Meiling, Wang, Yonghong, Liu, Xiaoling, Deng, Cunliang, Sun, Changfeng. 2024. Identification of RAD51AP1 as a key gene in hepatitis B virus-associated hepatocellular carcinoma. In Heliyon, 11, e41594. doi:10.1016/j.heliyon.2024.e41594. https://pubmed.ncbi.nlm.nih.gov/39850418/
4. Filipe, Alice, Katopodis, Periklis, Chudasama, Dimple, Hall, Marcia, Karteris, Emmanouil. 2022. Differential Expression of RAD51AP1 in Ovarian Cancer: Effects of siRNA In Vitro. In Journal of personalized medicine, 12, . doi:10.3390/jpm12020201. https://pubmed.ncbi.nlm.nih.gov/35207688/
5. Zhao, Hongyu, Gao, Yan, Chen, Qi, Zhao, Xiaoting, Yue, Wentao. 2020. RAD51AP1 promotes progression of ovarian cancer via TGF-β/Smad signalling pathway. In Journal of cellular and molecular medicine, 25, 1927-1938. doi:10.1111/jcmm.15877. https://pubmed.ncbi.nlm.nih.gov/33314567/
6. Huang, Xiaoyan, Wu, Zaixin, Xiao, Chunhong, Chen, X I. . E2F7/RAD51AP1 Axis Inhibits Endometrial Cancer Sensitivity to 5-FU via the Fatty Acid Metabolic Pathway. In Anticancer research, 43, 4905-4914. doi:10.21873/anticanres.16688. https://pubmed.ncbi.nlm.nih.gov/37909953/
7. Wei, Yongguang, Lan, Chenlu, Wang, Xiangkun, Peng, Tao, Zhu, Guangzhi. 2023. RAD51AP1 as an Immune-Related Prognostic Biomarker and Therapeutic Response Predictor in Hepatocellular Carcinoma. In International journal of general medicine, 16, 4377-4392. doi:10.2147/IJGM.S431206. https://pubmed.ncbi.nlm.nih.gov/37789880/