Dong Yang, Ma Wei-Ming, Shi Zhen-Duo, Zhang Zhi-Guo, Zhou Jia-He, Li Yang, Zhang Shao-Qi, Pang Kun, Li Bi-Bo, Zhang Wen-da, Fan Tao, Zhu Guang-Yuan, Xue Liang, Li Rui, Liu Ying, Hao Lin, Han Cong-Hui
Department of Urology, Xuzhou Central Hospital, Xuzhou, China.
Medical College of Soochow University, Suzhou, China.
Front Oncol. 2021 Jun 23;11:685980. doi: 10.3389/fonc.2021.685980. eCollection 2021.
Bladder urothelial carcinoma (BC) is a fatal invasive malignancy and the most common malignancy of the urinary system. In the current study, we investigated the function and mechanisms of Neuropilin-1 (NRP1), the co-receptor for vascular endothelial growth factor, in BC pathogenesis and progression. The expression of NRP1 was evaluated using data extracted from GEO and HPA databases and examined in BC cell lines. The effect on proliferation, apoptosis, angiogenesis, migration, and invasion of BC cells were validated after knockdown. After identifying differentially expressed genes (DEGs) induced by silencing, GO/KEGG and IPA bioinformatics analyses were performed and specific predicted pathways and targets were confirmed Additionally, the co-expressed genes and ceRNA network were predicted using data downloaded from CCLE and TCGA databases, respectively. High expression of NRP1 was observed in BC tissues and cells. knockdown promoted apoptosis and suppressed proliferation, angiogenesis, migration, and invasion of BC cells. Additionally, after silencing the activity of MAPK signaling and molecular mechanisms of cancer pathways were predicted by KEGG and IPA pathway analysis and validated using western blot in BC cells. knockdown also affected various biological functions, including antiviral response, immune response, cell cycle, proliferation and migration of cells, and neovascularisation. Furthermore, the main upstream molecule of the DEGs induced by knockdown may be , and was also the downstream target of and essential for regulation of expression to activate neovascularisation. was positively regulated by , and PPAR signaling was significantly associated with low expression. We also found that NRP1 was a predicted target of miR-204, miR-143, miR-145, and miR-195 in BC development. Our data provide evidence for the biological function and molecular aetiology of NRP1 in BC and for the first time demonstrated an association between NRP1 and NUPR1, FOXP3, and DCBLD2. Specifically, downregulation of contributes to BC progression, which is associated with activation of MAPK signaling and molecular mechanisms involved in cancer pathways. Therefore, NRP1 may serve as a target for new therapeutic strategies to treat BC and other cancers.
膀胱尿路上皮癌（BC）是一种致命的侵袭性恶性肿瘤，也是泌尿系统最常见的恶性肿瘤。在本研究中，我们调查了血管内皮生长因子的共受体神经纤毛蛋白-1（NRP1）在BC发病机制和进展中的作用及机制。使用从GEO和HPA数据库提取的数据评估NRP1的表达，并在BC细胞系中进行检测。敲低后验证了对BC细胞增殖、凋亡、血管生成、迁移和侵袭的影响。在鉴定出由沉默诱导的差异表达基因（DEG）后，进行了GO/KEGG和IPA生物信息学分析，并确认了特定的预测途径和靶点。此外，分别使用从CCLE和TCGA数据库下载的数据预测共表达基因和ceRNA网络。在BC组织和细胞中观察到NRP1的高表达。敲低促进了BC细胞的凋亡，并抑制了其增殖、血管生成、迁移和侵袭。此外，沉默后，通过KEGG和IPA途径分析预测了MAPK信号传导的活性和癌症途径的分子机制，并在BC细胞中使用蛋白质印迹法进行了验证。敲低还影响了各种生物学功能，包括抗病毒反应、免疫反应、细胞周期、细胞增殖和迁移以及新血管形成。此外，敲低诱导的DEG的主要上游分子可能是 ，并且 也是 的下游靶点，对调节 表达以激活新血管形成至关重要。 受 正调控，并且PPAR信号传导与低 表达显著相关。我们还发现，在BC发生发展过程中，NRP1是miR-204、miR-143、miR-145和miR-195的预测靶点。我们的数据为NRP1在BC中的生物学功能和分子病因提供了证据，并首次证明了NRP1与NUPR1、FOXP3和DCBLD2之间的关联。具体而言， 的下调促进了BC的进展，这与MAPK信号传导的激活和癌症途径中涉及的分子机制有关。因此，NRP1可能作为治疗BC和其他癌症的新治疗策略的靶点。
