Hu Yuanjun, Zhu Sihan, Xu Rizhen, Wang Manxia, Chen Furong, Zhang Zeshun, Feng Binghong, Wang Jian, Chen Zhongping, Wang Jing
State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
Department of Neurosurgery/Neuro-Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.
Front Genet. 2022 Oct 11;13:867872. doi: 10.3389/fgene.2022.867872. eCollection 2022.
Medulloblastoma is the most common pediatric malignant tumor in central nervous system. Although its prognosis has been improved enormously by the combination treatments with surgery, radiotherapy, and chemotherapy, it still could progress invasion and distant dissemination. We aimed to investigate molecular mechanisms of medulloblastoma invasion in the current work. The gene expression profile of medulloblastoma were analyzed based on the data deposited in Gene Expression Omnibus (GEO) and filtered according to brain specific proteins in the Uniprot. Delta-catenin was identified and further analyzed about its expression and roles in the prognosis of medulloblastoma patient. The function of delta-catenin on cell invasion and migration were investigated by transwell and wound healing assay. Whether delta-catenin participates in the epithelial-mesenchymal transition (EMT) regulated invasion was also studied. Delta-catenin expression was highly upregulated in tumor tissues compared to normal tissues from medulloblastoma patients in five independent, nonoverlapping cohorts. Furthermore, delta-catenin expression level was upregulated in WNT subgroup, and significantly correlated with better prognosis, and associated with metastasis through GEO database analysis. Functional assays indicated that delta-catenin inhibited medulloblastoma cell invasion and migration through regulating the key factors of EMT pathway, such as E-cadherin and vimentin. Delta-catenin might be a positive predictor for prognosis of medulloblastoma patients, through attenuating medulloblastoma cell invasion by inhibiting EMT pathway.
髓母细胞瘤是中枢神经系统中最常见的儿童恶性肿瘤。尽管通过手术、放疗和化疗的联合治疗,其预后有了极大改善,但它仍可能进展为侵袭和远处播散。在当前研究中,我们旨在探究髓母细胞瘤侵袭的分子机制。基于基因表达综合数据库(GEO)中存储的数据对髓母细胞瘤的基因表达谱进行分析,并根据通用蛋白质数据库(Uniprot)中的脑特异性蛋白质进行筛选。鉴定出δ-连环蛋白,并进一步分析其在髓母细胞瘤患者预后中的表达及作用。通过Transwell实验和伤口愈合实验研究δ-连环蛋白对细胞侵袭和迁移的作用。还研究了δ-连环蛋白是否参与上皮-间质转化(EMT)调控的侵袭过程。在五个独立、不重叠的队列中,与髓母细胞瘤患者的正常组织相比,肿瘤组织中δ-连环蛋白的表达高度上调。此外,通过GEO数据库分析,δ-连环蛋白在WNT亚组中的表达水平上调,且与较好的预后显著相关,并与转移有关。功能实验表明,δ-连环蛋白通过调节EMT途径的关键因子,如E-钙黏蛋白和波形蛋白,抑制髓母细胞瘤细胞的侵袭和迁移。δ-连环蛋白可能是髓母细胞瘤患者预后的一个积极预测指标,它通过抑制EMT途径减弱髓母细胞瘤细胞的侵袭。