SEM1 promotes tumor progression of glioblastoma via activating the akt signaling pathway

Chuntao Li; Bo Chen; Junxia Zhang; Jingxuan Yang; Muzi Guo; Yu Ren; Zhijun Zhou; Kar-Ming Fung; Min Li; Liyang Zhang; Zhixiong Liu

doi:10.1016/j.canlet.2023.216368

SEM1 promotes tumor progression of glioblastoma via activating the akt signaling pathway

Cancer Lett. 2023 Nov 28:577:216368. doi: 10.1016/j.canlet.2023.216368. Epub 2023 Aug 29.

Authors

Chuntao Li¹, Bo Chen², Junxia Zhang³, Jingxuan Yang⁴, Muzi Guo⁴, Yu Ren⁴, Zhijun Zhou⁴, Kar-Ming Fung⁵, Min Li⁶, Liyang Zhang⁷, Zhixiong Liu⁸

Affiliations

¹ 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.
² 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.
³ Department of Medicine, And Department of Surgery, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA; Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Guangzhou Road 300, Nanjing, 210029, China.
⁴ Department of Medicine, And Department of Surgery, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA.
⁵ Department of Pathology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA.
⁶ Department of Medicine, And Department of Surgery, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA. Electronic address: min-li@ouhsc.edu.
⁷ 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; Hypothalamic-pituitary Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, PR China. Electronic address: zhangliyang@csu.edu.cn.
⁸ 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. Electronic address: zhixiongliu@csu.edu.cn.

PMID: 37652287
DOI: 10.1016/j.canlet.2023.216368

Abstract

Introduction: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: Apoptosis; Drug; Glioma; Invasion; Migration; Prognosis; Proliferation; SEM1.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Apoptosis
Cell Line, Tumor
Cell Movement
Cell Proliferation
Glioblastoma* / genetics
Glioblastoma* / pathology
Glioma* / pathology
Humans
Molecular Docking Simulation
Phosphatidylinositol 3-Kinases / metabolism
Proto-Oncogene Proteins c-akt / metabolism
Signal Transduction

Substances

Proto-Oncogene Proteins c-akt
Phosphatidylinositol 3-Kinases