BCAS2，一种在晚期前列腺癌中富集的蛋白质，与 NBS1 相互作用以增强 DNA 双链断裂修复。
BCAS2, a protein enriched in advanced prostate cancer, interacts with NBS1 to enhance DNA double-strand break repair.
机构信息
Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Graduate Institute of Medical Genomics and Proteomics, College of Medicine, National Taiwan University, Taipei, Taiwan.
出版信息
Br J Cancer. 2020 Dec;123(12):1796-1807. doi: 10.1038/s41416-020-01086-y. Epub 2020 Sep 23.
BACKGROUND
Breast cancer amplified sequence 2 (BCAS2) plays crucial roles in pre-mRNA splicing and androgen receptor transcription. Previous studies suggested that BCAS2 is involved in double-strand breaks (DSB); therefore, we aimed to characterise its mechanism and role in prostate cancer (PCa).
METHODS
Western blotting and immunofluorescence microscopy were used to assay the roles of BCAS2 in the DSBs of PCa cells and apoptosis in Drosophila, respectively. The effect of BCAS2 dosage on non-homologous end joining (NHEJ) and homologous recombination (HR) were assayed by precise end-joining assay and flow cytometry, respectively. Glutathione-S-transferase pulldown and co-immunoprecipitation assays were used to determine whether and how BCAS2 interacts with NBS1. The expression of BCAS2 and other proteins in human PCa was determined by immunohistochemistry.
RESULTS
BCAS2 helped repair radiation-induced DSBs efficiently in both human PCa cells and Drosophila. BCAS2 enhanced both NHEJ and HR, possibly by interacting with NBS1, which involved the BCAS2 N-terminus as well as both the NBS1 N- and C-termini. The overexpression of BCAS2 was significantly associated with higher Gleason and pathology grades and shorter survival in patients with PCa.
CONCLUSION
BCAS2 promotes two DSB repair pathways by interacting with NBS1, and it may affect PCa progression.
背景
乳腺癌扩增序列 2（BCAS2）在 mRNA 前体剪接和雄激素受体转录中发挥关键作用。先前的研究表明，BCAS2 参与双链断裂（DSB）；因此，我们旨在研究其在前列腺癌（PCa）中的机制和作用。
方法
使用 Western blot 和免疫荧光显微镜分别检测 BCAS2 在 PCa 细胞 DSB 和果蝇细胞凋亡中的作用。通过精确末端连接测定和流式细胞术分别检测 BCAS2 剂量对非同源末端连接（NHEJ）和同源重组（HR）的影响。使用谷胱甘肽-S-转移酶下拉和免疫共沉淀测定来确定 BCAS2 是否以及如何与 NBS1 相互作用。通过免疫组织化学测定来确定 BCAS2 和其他蛋白质在人前列腺癌中的表达。
结果
BCAS2 有助于有效地修复人 PCa 细胞和果蝇中辐射诱导的 DSB。BCAS2 增强了 NHEJ 和 HR，可能通过与 NBS1 相互作用，涉及 BCAS2 的 N 端以及 NBS1 的 N 和 C 端。BCAS2 的过表达与 PCa 患者更高的 Gleason 评分和病理分级以及更短的生存时间显著相关。
结论
BCAS2 通过与 NBS1 相互作用促进两种 DSB 修复途径，可能影响 PCa 的进展。
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