Department of Neurosurgery, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008, China; Department of Medicine, And Department of Surgery, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA.
Department of Neurosurgery, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008, China; Hypothalamic-pituitary Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, PR China; Department of Surgery, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong SAR, China.
Cancer Lett. 2023 Nov 28;577:216368. doi: 10.1016/j.canlet.2023.216368. Epub 2023 Aug 29.
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.
SEMI，一种 26S 蛋白酶体复合物亚基，是肿瘤生长的重要调节因子。然而，SEMI 介导的胶质瘤进展的潜在机制仍有待阐明。
分析了肿瘤块、单细胞和空间测序的数据，以揭示 SEMI 与胶质瘤临床特征、细胞类型和功能富集之间的相关性。免疫组织化学用于评估 SEMI 的表达。MTT、流式细胞术、细胞凋亡特征、上皮-间充质转化特征、Transwell 和类器官测定用于研究 SEMI 对胶质瘤（U251 和 LN229）细胞恶性行为的影响。进行加权基因共表达网络分析（WGCNA）以构建 SEMI 介导的恶性调节网络。相应地进行了生存分析、治疗反应、药物预测和分子对接分析。
在胶质瘤中观察到高 SEMI 表达，与较差的临床特征和预后相关。此外，SEMI 主要定位于恶性细胞（胶质瘤细胞）中。SEMI 敲除抑制了胶质瘤细胞的增殖、侵袭和迁移，并促进了其凋亡。我们还构建了一个 SEMI 恶性调节网络，该网络由 PI3K-Akt 通路连接。该网络具有很高的预后价值。最后，筛选了可能靶向 SEMI 的药物并对 SEMI 进行了对接。
SEMI 参与了胶质瘤细胞的增殖、凋亡、侵袭和迁移。SEMI 恶性调节网络对胶质瘤的预后和治疗具有重要意义。
