SEM1是26S蛋白酶体复合物亚单位，是肿瘤生长的重要调节因子。然而，SEM1介导的胶质瘤进展的潜在机制尚不清楚。我们分析了批量肿瘤、单细胞和空间测序的数据，以揭示SEM1与胶质瘤的临床特征、细胞类型和功能富集之间的相关性。我们使用免疫组化来评估SEM1的表达。我们利用MTT、流式细胞术、凋亡标记、上皮-间质转化标记、Transwell和有机体实验来研究SEM1对胶质瘤（U251和LN229）细胞的恶性行为的影响。我们进行了加权基因共表达网络分析（WGCNA），构建了一个SEM1调节的恶性网络。相应地，我们进行了生存分析、治疗反应、药物预测和分子对接分析。我们观察到胶质瘤中SEM1的高表达，并且与较差的临床特征和预后相关。此外，SEM1主要定位在恶性细胞（胶质瘤细胞）中。SEM1敲除抑制了胶质瘤细胞的增殖、侵袭和迁移，并促进了它们的凋亡。我们还构建了一个通过PI3K-Akt通路连接的SEM1恶性调节网络。这个网络具有很高的预后价值。最后，我们筛选并对接到SEM1的潜在靶向药物。SEM1在胶质瘤细胞的增殖、凋亡、侵袭和迁移中起着关键作用。SEM1恶性调节网络对胶质瘤的预后和治疗具有重要意义。版权所有©2023年Elsevier B.V.出版。

SEM1, a 26 S proteasome complex subunit, is an essential regulator of tumor growth. However, the underlying mechanism of SEM1 mediated glioma progression remains to be elucidated.Data from bulk-tumor, single-cell, and spatial sequencing were analyzed to reveal correlations between SEM1 and clinical traits, cell types, and functional enrichment in gliomas. Immunohistochemistry was used to assess SEM1 expression. MTT, flow cytometry, apoptosis signature, epithelial-mesenchymal transition signature, Transwell, and organoid assays were used to study SEM1's effect on the malignant behavior of glioma (U251 and LN229) cells. Weighted gene co-expression network analysis (WGCNA) was conducted to construct an SEM1-mediated malignant regulatory network. Accordingly, survival analysis, therapeutic response, drug prediction, and molecular docking analyses were performed.High SEM1 expression was observed in gliomas and correlated with worse clinical features and prognosis. Moreover, SEM1 is mainly localized in malignant cells (glioma cells). SEM1 knockout inhibited the proliferation, invasion, and migration of glioma cells and promoted their apoptosis. We also constructed an SEM1 malignant regulatory network that was bridged by the PI3K-Akt pathway. The network had a high prognostic value. Finally, drugs potentially targeting SEM1 were screened and docked to SEM1.SEM1 is critically involved in the proliferation, apoptosis, invasion, and migration of glioma cells. The SEM1 malignant regulatory network shows high significance for the prognosis and treatment of gliomas.Copyright © 2023. Published by Elsevier B.V.