Zhang Wenwu, Xiao Yuhan, Zhu Xin, Zhang Yanxia, Xiang Qin, Wu Shunhong, Song Xiaoyu, Zhao Junxiu, Yuan Ruanfei, Li Qiguang, Xiao Bin, Li Linhai
Department of Laboratory Medicine, The Affiliated Qingyuan Hospital (Qingyuan People's Hospital), Guangzhou Medical University, Qingyuan, Guangdong, 511518, People's Republic of China.
Department of Laboratory Medicine, Suzhou Municipal Hospital, Affiliated to Nanjing Medical University, Suzhou, 21500, People's Republic of China.
J Inflamm Res. 2024 Jul 17;17:4721-4746. doi: 10.2147/JIR.S458832. eCollection 2024.
Meiotic nuclear division 1 (MND1) is a meiosis-specific protein that promotes lung adenocarcinoma progression. However, its expression and biological function across cancers remain largely unexplored.
The expression, prognostic significance, mutation status, and methylation profile of MND1 in various cancers were comprehensively analyzed using the TIMER, GTEX, Kaplan-Meier plotter, cBioPortal, and GSCA databases. Additionally, we constructed a PPI network, enrichment analysis and single-cell transcriptomic sequencing to elucidate the underlying mechanism of MND1. Furthermore, we investigated the association between MND1 expression and drug sensitivity using CellMiner. Moreover, we also explored the correlation between MND1 expression and immune infiltration. Finally, we validated the functional role of MND1 in breast cancer through IHC staining, CCK8, EdU, colony formation, and flow cytometry assays.
MND1 has been reported to be highly expressed in Pan-cancer, High MND1 expression was significantly associated with poor prognosis in cancers. Additionally, MND1 mutation frequency is high in most cancers, and its expression correlates with methylation. Furthermore, MND1 expression significantly correlates with immune checkpoint blockade (ICB) markers, including PD-L1, PD-1, and CTLA-4. The PPI network reveals interactions between MND1 and PSMC3IP, BRCA1, and BRCA2. Enrichment analysis and single-cell sequencing indicate that MND1 positively correlates with cell cycle. ROC curve reveals favorable diagnostic efficacy of MND1 in breast cancer. In vitro, MND1 overexpression promotes breast cancer cell proliferation and increases the expression of key cell cycle regulators (CDK4, CDK6, and cyclin D3), accelerating the G1/S phase transition and leading to abnormal breast cancer cell proliferation. The immunohistochemical analysis revealed a robust expression of MND1 in breast cancer tissues, exhibiting a significant positive correlation with PD-L1 and FOXP3.
MND1 is an oncogene and may serve as a biomarker for cancer prognosis and immunotherapy. Targeting MND1 may be a potential tumor treatment strategy.
减数分裂核分裂1（MND1）是一种促进肺腺癌进展的减数分裂特异性蛋白。然而，其在各种癌症中的表达及生物学功能仍 largely未被探索。
使用TIMER、GTEX、Kaplan-Meier Plotter、cBioPortal和GSCA数据库全面分析了MND1在各种癌症中的表达、预后意义、突变状态和甲基化谱。此外，我们构建了蛋白质-蛋白质相互作用（PPI）网络、富集分析和单细胞转录组测序以阐明MND1的潜在机制。此外，我们使用CellMiner研究了MND1表达与药物敏感性之间的关联。此外，我们还探讨了MND1表达与免疫浸润之间的相关性。最后，我们通过免疫组化染色、CCK8、EdU、集落形成和流式细胞术检测验证了MND1在乳腺癌中的功能作用。
据报道，MND1在泛癌中高表达，MND1高表达与癌症预后不良显著相关。此外，MND1在大多数癌症中的突变频率较高，其表达与甲基化相关。此外，MND1表达与免疫检查点阻断（ICB）标志物，包括程序性死亡受体配体1（PD-L1）、程序性死亡受体1（PD-1）和细胞毒性T淋巴细胞相关蛋白4（CTLA-4）显著相关。PPI网络揭示了MND1与蛋白酶体26S亚基非ATP酶调节因子3相互作用蛋白（PSMC3IP）、乳腺癌1号基因（BRCA1）和乳腺癌2号基因（BRCA2）之间的相互作用。富集分析和单细胞测序表明MND1与细胞周期呈正相关。ROC曲线显示MND1在乳腺癌中有良好的诊断效能。在体外，MND1过表达促进乳腺癌细胞增殖并增加关键细胞周期调节因子（细胞周期蛋白依赖性激酶4（CDK4）、细胞周期蛋白依赖性激酶6（CDK6）和细胞周期蛋白D3）的表达，加速G1/S期转换并导致乳腺癌细胞异常增殖。免疫组化分析显示MND1在乳腺癌组织中表达强烈，与PD-L1和叉头框蛋白P3（FOXP3）呈显著正相关。
MND1是一种癌基因，可能作为癌症预后和免疫治疗的生物标志物。靶向MND1可能是一种潜在的肿瘤治疗策略。
