RAD51AP1在卵巢癌中的差异表达：siRNA的体外作用
Differential Expression of RAD51AP1 in Ovarian Cancer: Effects of siRNA In Vitro.
作者信息
Filipe Alice, Katopodis Periklis, Chudasama Dimple, Kerslake Rachel, Jeyaneethi Jeyarooban, Anikin Vladimir, Silva Elisabete, Kyrou Ioannis, Randeva Harpal S, Sisu Cristina, Hall Marcia, Karteris Emmanouil
机构信息
Department of Life Sciences, Division of Biosciences, College of Health, Medicine and Life Sciences, Brunel University London, Uxbridge UB8 3PH, UK.
Division of Thoracic Surgery, The Royal Brompton & Harefield NHS Foundation Trust, Harefield Hospital, Harefield UB9 6JH, UK.
出版信息
J Pers Med. 2022 Feb 1;12(2):201. doi: 10.3390/jpm12020201.
BACKGROUND
DNA double strand breaks can affect genome integrity potentially leading to cancer. RAD51-associated protein 1 (RAD51AP1), an accessory protein to RAD51, is critical for homologous recombination, a key DNA damage response pathway. Emerging studies indicate a novel role for RAD51AP1 in carcinogenesis. Here we provide additional insight into the role of RAD51AP1 in ovarian cancer (OvCa).
METHODS
Gene expression and patient phenotype data were obtained from TCGA and GTEX project consortia for bioinformatics analysis. Immunohistochemistry of OvCa tissue microarray was undertaken. Functional analyses were performed in a SKOV3 OvCa cell line with down-regulation of RAD51AP1 using siRNA.
RESULTS
RAD51AP1 is overexpressed at gene level in primary and recurrent OvCa compared to controls. At protein level, RAD51AP1 was up-regulated in low grade serous tumors compared to high grade OvCa. There was higher expression of RAD51AP1 in OvCa metastatic to lymph nodes compared to primary cancer samples. Gene enrichment analyses identified 12 differentially expressed genes (DEGs) related to OvCa, eight of which are also common in tissue from patients with type 2 diabetes mellitus (T2DM).
CONCLUSIONS
RAD51AP1 is overexpressed in OvCa, Given the link between OvCa and T2DM, the eight-gene signature shows potential for predictive value.
背景
DNA双链断裂会影响基因组完整性，可能导致癌症。RAD51相关蛋白1（RAD51AP1）是RAD51的一种辅助蛋白，对同源重组至关重要，同源重组是一种关键的DNA损伤反应途径。新出现的研究表明RAD51AP1在致癌过程中具有新作用。在此，我们对RAD51AP1在卵巢癌（OvCa）中的作用提供了更多见解。
方法
从TCGA和GTEX项目联盟获取基因表达和患者表型数据进行生物信息学分析。对OvCa组织微阵列进行免疫组织化学分析。使用小干扰RNA（siRNA）在RAD51AP1下调的SKOV3卵巢癌细胞系中进行功能分析。
结果
与对照组相比，RAD51AP1在原发性和复发性OvCa的基因水平上过度表达。在蛋白质水平上，与高级别OvCa相比，RAD51AP1在低级别浆液性肿瘤中上调。与原发性癌样本相比，转移至淋巴结的OvCa中RAD51AP1表达更高。基因富集分析确定了12个与OvCa相关的差异表达基因（DEG），其中8个在2型糖尿病（T2DM）患者的组织中也很常见。
结论
RAD51AP1在OvCa中过度表达，鉴于OvCa与T2DM之间的联系，这8个基因特征显示出具有预测价值的潜力。
Zotero 插件