State Key Laboratory of Reproductive Medicine, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing 211116, China.
Cancer Biol Med. 2021 Feb 15;18(1):74-87. doi: 10.20892/j.issn.2095-3941.2020.0071.
The newly defined cancer-testis (CT) gene, was previously found to play key roles in DNA double-strand break (DSB) repair. In this study, we aimed to investigate the effects and mechanisms of MEIOB in the carcinogenesis of triple-negative breast cancers (TNBCs).
The Cancer Genome Atlas database was used to quantify the expression of . Cox regression analysis was used to evaluate the association between expression and the prognosis of human TNBC. The effects of MEIOB on cell proliferation and migration in TNBCs were also assessed . Patient-derived xenograft (PDX) models were used to assess the sensitivity of breast cancers with active MEIOB to PARP1 inhibitors.
We confirmed as a CT gene whose expression was restricted to the testes and breast tumors, especially TNBCs. Its activation was significantly associated with poor survival in breast cancer patients [overall, hazard ratio (HR) = 1.90 (1.16-2.06); TNBCs: HR = 7.05 (1.16-41.80)]. In addition, we found that was oncogenic and significantly promoted the proliferation of TNBC cells. Further analysis showed that participated in DSB repair in TNBCs. However, in contrast to its function in meiosis, it mediated homologous recombination deficiency (HRD) through the activation of polyADP-ribose polymerase (PARP)1 by interacting with YBX1. Furthermore, activated MEIOB was shown to confer sensitivity to PARP inhibitors, which was confirmed in PDX models.
played an oncogenic role in TNBC through its involvement in HRD. In addition, dysregulation of sensitized TNBC cells to PARP inhibitors, so may be a therapeutic target of PARP1 inhibitors in TNBC.
新定义的癌症睾丸（CT）基因 先前被发现在 DNA 双链断裂（DSB）修复中发挥关键作用。本研究旨在探讨 MEIOB 在三阴性乳腺癌（TNBC）发生中的作用和机制。
使用癌症基因组图谱数据库来量化 的表达。Cox 回归分析用于评估 表达与人类 TNBC 预后之间的关联。还评估了 MEIOB 对 TNBC 细胞增殖和迁移的影响。使用患者来源的异种移植（PDX）模型来评估具有活跃 MEIOB 的乳腺癌对 PARP1 抑制剂的敏感性。
我们证实 是一种 CT 基因，其表达仅限于睾丸和乳腺癌肿瘤，特别是 TNBC。其激活与乳腺癌患者的不良生存显著相关[总体而言，风险比（HR）=1.90（1.16-2.06）；TNBC：HR=7.05（1.16-41.80）]。此外，我们发现 是致癌的，并且显著促进了 TNBC 细胞的增殖。进一步分析表明， 在 TNBC 中参与 DSB 修复。然而，与减数分裂中的功能相反，它通过与 YBX1 相互作用激活聚 ADP-核糖聚合酶（PARP）1 来介导同源重组缺陷（HRD）。此外，激活的 MEIOB 被证明对 PARP 抑制剂敏感，这在 PDX 模型中得到了证实。
通过参与 HRD 在 TNBC 中发挥致癌作用。此外， 的失调使 TNBC 细胞对 PARP 抑制剂敏感，因此 可能是 TNBC 中 PARP1 抑制剂的治疗靶点。
