Reference Citation Analysis: Find an Article, Find a Category, Find a Journal, Find a Scholar

For: Zhou D, Alver BM, Li S, Hlady RA, Thompson JJ, Schroeder MA, Lee JH, Qiu J, Schwartz PH, Sarkaria JN, Robertson KD. Distinctive epigenomes characterize glioma stem cells and their response to differentiation cues. Genome Biol 2018;19:43. [PMID: 29587824 PMCID: PMC5872397 DOI: 10.1186/s13059-018-1420-6] [Citation(s) in RCA: 57] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [What about the content of this article? (0)] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2017] [Accepted: 03/12/2018] [Indexed: 01/06/2023] Open

For:	Zhou D, Alver BM, Li S, Hlady RA, Thompson JJ, Schroeder MA, Lee JH, Qiu J, Schwartz PH, Sarkaria JN, Robertson KD. Distinctive epigenomes characterize glioma stem cells and their response to differentiation cues. Genome Biol 2018;19:43. [PMID: 29587824 PMCID: PMC5872397 DOI: 10.1186/s13059-018-1420-6] [Citation(s) in RCA: 57] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [What about the content of this article? (0)] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2017] [Accepted: 03/12/2018] [Indexed: 01/06/2023] Open

Number

Cited by Other Article(s)

Geng J, Shao Y, Pu Y, Wu Y, Yang Z. Transcription Factor CEBPD-Mediated WTAP Facilitates the Stemness, Growth, Migration and Glycolysis of Glioblastoma Stem Like Cells. Neurochem Res 2025;50:100. [PMID: 39945969 DOI: 10.1007/s11064-024-04321-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2024] [Revised: 11/26/2024] [Accepted: 12/17/2024] [Indexed: 04/26/2025]

Wroblewski TH, Karabacak M, Seah C, Yong RL, Margetis K. Radiomic Consensus Clustering in Glioblastoma and Association with Gene Expression Profiles. Cancers (Basel) 2024;16:4256. [PMID: 39766155 PMCID: PMC11674874 DOI: 10.3390/cancers16244256] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2024] [Revised: 12/16/2024] [Accepted: 12/18/2024] [Indexed: 01/11/2025] Open

Abstract

BACKGROUND/OBJECTIVES

Glioblastoma (GBM) is the most common malignant primary central nervous system tumor with extremely poor prognosis and survival outcomes. Non-invasive methods like radiomic feature extraction, which assess sub-visual imaging features, provide a potentially powerful tool for distinguishing molecular profiles across groups of patients with GBM. Using consensus clustering of MRI-based radiomic features, this study aims to investigate differential gene expression profiles based on radiomic clusters.

METHODS

Patients from the TCGA and CPTAC datasets (n = 114) were included in this study. Radiomic features including T1, T1 with contrast, T2, and FLAIR MRI sequences were extracted using PyRadiomics. Selected radiomic features were then clustered using ConsensusClusterPlus (k-means base algorithm and Euclidean distance), which iteratively subsamples and clusters 80% of the data to identify stable clusters by calculating the frequency in which each patient is a member of a cluster across iterations. Gene expression data (available for n = 69 patients) was analyzed using differential gene expression (DEG) and gene set enrichment (GSEA) approaches, after batch correction using ComBat-seq.

RESULTS

Three distinct clusters were identified based on the relative consensus matrix and cumulative distribution plots (Cluster 1, n = 25; Cluster 2, n = 46; Cluster 3, n = 43). No significant differences in patient demographic characteristics, MGMT methylation status, tumor location, or overall survival were identified across clusters. Differentially expressed genes were identified in Cluster 1, which have been previously associated with GBM prognosis, recurrence, and treatment sensitivity. GSEA of Cluster 1 showed an enrichment of genes upregulated for immune-related and DNA metabolism pathways and genes downregulated in pathways associated with protein and histone deacetylation. Clusters 2 and 3 exhibited fewer DEGs which failed to reach significance after multiple testing corrections.

CONCLUSIONS

Consensus clustering of radiomic features revealed unique gene expression profiles in the GBM cohort which likely represent subtle differences in tumor biology and radiosensitivity that are not visually discernible, underscoring the potential of radiomics to serve as a non-invasive alternative for identifying GBM molecular heterogeneity. Further investigation is still required to validate these findings and their clinical implications.

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Xu Q, Yang C, Wang L, Zhou J. Unveiling the role of RNA methylation in glioma: Mechanisms, prognostic biomarkers, and therapeutic targets. Cell Signal 2024;124:111380. [PMID: 39236835 DOI: 10.1016/j.cellsig.2024.111380] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2024] [Revised: 08/30/2024] [Accepted: 09/01/2024] [Indexed: 09/07/2024]

Lucchini S, Constantinou M, Marino S. Unravelling the mosaic: Epigenetic diversity in glioblastoma. Mol Oncol 2024;18:2871-2889. [PMID: 39148319 PMCID: PMC11619803 DOI: 10.1002/1878-0261.13706] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2023] [Revised: 06/21/2024] [Accepted: 07/23/2024] [Indexed: 08/17/2024] Open

Prakash V, Gabrani R. Epigenetic dysregulation in glioblastoma: potential pathways to precision medicine. Neurogenetics 2024;26:5. [PMID: 39585441 DOI: 10.1007/s10048-024-00793-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2024] [Accepted: 09/11/2024] [Indexed: 11/26/2024]

Wu M, Wang T, Ji N, Lu T, Yuan R, Wu L, Zhang J, Li M, Cao P, Zhao J, Li G, Li J, Li Y, Tang Y, Gao Z, Wang X, Cheng W, Ge M, Cui G, Li R, Wu A, You Y, Zhang W, Wang Q, Chen J. Multi-omics and pharmacological characterization of patient-derived glioma cell lines. Nat Commun 2024;15:6740. [PMID: 39112531 PMCID: PMC11306361 DOI: 10.1038/s41467-024-51214-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2023] [Accepted: 07/31/2024] [Indexed: 08/10/2024] Open

Affiliation(s)

Min Wu Chinese Institute for Brain Research, Beijing, Research Unit of Medical Neurobiology, Chinese Academy of Medical Sciences, Beijing, China Institute of Functional Nano & Soft Materials (FUNSOM), Soochow University, Suzhou, China Shanghai Immune Therapy Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China Department of Bioinformatics, Nanjing Medical University, Nanjing, China Institute for Brain Tumors, Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China
Tingting Wang Chinese Institute for Brain Research, Beijing, Research Unit of Medical Neurobiology, Chinese Academy of Medical Sciences, Beijing, China Changping Laboratory, Beijing, China Chinese Institute for Brain Research, Beijing, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
Nan Ji Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
Ting Lu Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, China
Ran Yuan Chinese Institute for Brain Research, Beijing, Research Unit of Medical Neurobiology, Chinese Academy of Medical Sciences, Beijing, China Institute of Functional Nano & Soft Materials (FUNSOM), Soochow University, Suzhou, China
Lingxiang Wu Department of Bioinformatics, Nanjing Medical University, Nanjing, China Institute for Brain Tumors, Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, China
Junxia Zhang Institute for Brain Tumors, Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
Mengyuan Li Chinese Institute for Brain Research, Beijing, Research Unit of Medical Neurobiology, Chinese Academy of Medical Sciences, Beijing, China Changping Laboratory, Beijing, China
Penghui Cao Chinese Institute for Brain Research, Beijing, Research Unit of Medical Neurobiology, Chinese Academy of Medical Sciences, Beijing, China
Jiarui Zhao Chinese Institute for Brain Research, Beijing, Research Unit of Medical Neurobiology, Chinese Academy of Medical Sciences, Beijing, China
Guanzhang Li Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China Department of Molecular Neuropathology, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China
Jianyu Li Chinese Institute for Brain Research, Beijing, Research Unit of Medical Neurobiology, Chinese Academy of Medical Sciences, Beijing, China
Yu Li Chinese Institute for Brain Research, Beijing, Research Unit of Medical Neurobiology, Chinese Academy of Medical Sciences, Beijing, China
Yujie Tang Shanghai Key Laboratory of Reproductive Medicine, Department of Histoembryology, Genetics and Developmental Biology, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Zhengliang Gao Fundamental Research Center, Shanghai YangZhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), School of Medicine, Tongji University, Shanghai, China Institute of Geriatrics (Shanghai University), Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong), School of Medicine, Shanghai University, Nantong, China Department of Anesthesiology, Gongli Hospital of Shanghai Pudong New Area, Shanghai, China
Xiuxing Wang National Health Commission Key Laboratory of Antibody Techniques, Department of Cell Biology, Jiangsu Provincial Key Laboratory of Human Functional Genomics, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, China
Wen Cheng Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, China
Ming Ge Department of Neurosurgery, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China
Gang Cui Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, China
Rui Li Department of Neurosurgery, China-Japan Friendship Hospital, No. 2 Yinghua East Road, Chaoyang District, Beijing, China
Anhua Wu Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, China
Yongping You Institute for Brain Tumors, Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China. Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Wei Zhang Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China. China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China. Department of Molecular Neuropathology, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.
Qianghu Wang Department of Bioinformatics, Nanjing Medical University, Nanjing, China. Institute for Brain Tumors, Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China. The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, China.
Jian Chen Chinese Institute for Brain Research, Beijing, Research Unit of Medical Neurobiology, Chinese Academy of Medical Sciences, Beijing, China. Changping Laboratory, Beijing, China. Chinese Institute for Brain Research, Beijing, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.

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Yap CX, Vo DD, Heffel MG, Bhattacharya A, Wen C, Yang Y, Kemper KE, Zeng J, Zheng Z, Zhu Z, Hannon E, Vellame DS, Franklin A, Caggiano C, Wamsley B, Geschwind DH, Zaitlen N, Gusev A, Pasaniuc B, Mill J, Luo C, Gandal MJ. Brain cell-type shifts in Alzheimer's disease, autism, and schizophrenia interrogated using methylomics and genetics. SCIENCE ADVANCES 2024;10:eadn7655. [PMID: 38781333 PMCID: PMC11114225 DOI: 10.1126/sciadv.adn7655] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/27/2023] [Accepted: 03/14/2024] [Indexed: 05/25/2024]

Affiliation(s)

Chloe X. Yap Mater Research Institute, University of Queensland, Brisbane, Queensland, Australia Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia Department of Psychiatry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA Program in Neurobehavioral Genetics, Semel Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA
Daniel D. Vo Department of Psychiatry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA Program in Neurobehavioral Genetics, Semel Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA Lifespan Brain Institute at Penn Medicine and The Children’s Hospital of Philadelphia, Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
Matthew G. Heffel Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA Bioinformatics Interdepartmental Program, University of California Los Angeles, Los Angeles, CA, USA
Arjun Bhattacharya Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA Institute for Quantitative and Computational Biosciences, David Geffen School of Medicine, University of California, Los Angeles, CA, USA Department of Epidemiology, University of Texas MD Anderson Cancer Center, Houston, TX, USA Institute for Data Science in Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA
Cindy Wen Department of Psychiatry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA Program in Neurobehavioral Genetics, Semel Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA
Yuanhao Yang Mater Research Institute, University of Queensland, Brisbane, Queensland, Australia Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia
Kathryn E. Kemper Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia
Jian Zeng Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia
Zhili Zheng Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia
Zhihong Zhu Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia The National Centre for Register-based Research, Aarhus University, Denmark
Eilis Hannon Department of Clinical and Biomedical Sciences, University of Exeter Medical School, University of Exeter, Exeter, UK
Dorothea Seiler Vellame Department of Clinical and Biomedical Sciences, University of Exeter Medical School, University of Exeter, Exeter, UK
Alice Franklin Department of Clinical and Biomedical Sciences, University of Exeter Medical School, University of Exeter, Exeter, UK
Christa Caggiano Bioinformatics Interdepartmental Program, University of California Los Angeles, Los Angeles, CA, USA Department of Neurology, University of California Los Angeles, Los Angeles, CA, USA
Brie Wamsley Department of Psychiatry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA Program in Neurobehavioral Genetics, Semel Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA Department of Neurology, University of California Los Angeles, Los Angeles, CA, USA Center for Autism Research and Treatment, Semel Institute, University of California, Los Angeles, Los Angeles, CA, USA
Daniel H. Geschwind Department of Psychiatry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA Program in Neurobehavioral Genetics, Semel Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA Department of Neurology, University of California Los Angeles, Los Angeles, CA, USA Center for Autism Research and Treatment, Semel Institute, University of California, Los Angeles, Los Angeles, CA, USA
Noah Zaitlen Department of Neurology, University of California Los Angeles, Los Angeles, CA, USA Department of Computational Medicine, University of California Los Angeles, Los Angeles, CA, USA
Alexander Gusev Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA Division of Genetics, Brigham & Women’s Hospital, Boston, MA, USA Medical and Population Genetics, Broad Institute, Cambridge, MA, USA
Bogdan Pasaniuc Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA Bioinformatics Interdepartmental Program, University of California Los Angeles, Los Angeles, CA, USA Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA Department of Computational Medicine, University of California Los Angeles, Los Angeles, CA, USA Institute for Precision Health, University of California, Los Angeles, Los Angeles, CA, USA
Jonathan Mill Department of Clinical and Biomedical Sciences, University of Exeter Medical School, University of Exeter, Exeter, UK
Chongyuan Luo Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA
Michael J. Gandal Department of Psychiatry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA Program in Neurobehavioral Genetics, Semel Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA Lifespan Brain Institute at Penn Medicine and The Children’s Hospital of Philadelphia, Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

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Wu H, Yang Z, Chang C, Wang Z, Zhang D, Guo Q, Zhao B. A novel disulfide death-related genes prognostic signature identifies the role of IPO4 in glioma progression. Cancer Cell Int 2024;24:168. [PMID: 38734657 PMCID: PMC11088110 DOI: 10.1186/s12935-024-03358-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2023] [Accepted: 05/06/2024] [Indexed: 05/13/2024] Open

Abstract

BACKGROUND

"Disulfide death," a form of cellular demise, is triggered by the abnormal accumulation of intracellular disulfides under conditions of glucose deprivation. However, its role in the prognosis of glioma remains undetermined. Therefore, the main objective of this study is to establish prognostic signature based on disulfide death-related genes (DDRGs) and to provide new solutions in choosing the effective treatment of glioma.

METHODS

The RNA transcriptome, clinical information, and mutation data of glioma samples were sourced from The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA), while normal samples were obtained from the Genotype-Tissue Expression (GTEx). DDRGs were compiled from previous studies and selected through differential analysis and univariate Cox regression analysis. The molecular subtypes were determined through consensus clustering analysis. Further, LASSO analysis was employed to select characteristic genes, and subsequently, a risk model comprising seven DDRGs was constructed based on multivariable Cox analysis. Kaplan-Meier survival curves were employed to assess survival differences between high and low-risk groups. Additionally, functional analyses (GO, KEGG, GSEA) were conducted to explore the potential biological functions and signaling pathways of genes associated with the model. The study also explored immune checkpoint (ICP) genes, immune cell infiltration levels, and immune stromal scores. Finally, the effect of Importin-4(IPO4) on glioma has been further confirmed through RT-qPCR, Western blot, and cell functional experiments.

RESULTS

7 genes associated with disulfide death were obtained and two subgroups of patients with different prognosis and clinical characteristics were identified. Risk signature was subsequently developed and proved to serve as an prognostic predictor. Notably, the high-risk group exhibited an immunosuppressive microenvironment characterized by a high concentration of M2 macrophages and regulatory T cells (Tregs). In contrast, the low-risk group showed lower half-maximal inhibitory concentration (IC50) values. Therefore, patients in the high-risk group may benefit more from immunotherapy, while patients in the low-risk group may benefit more from chemotherapy. In addition, in vitro experiments have shown that inhibition of the expression of IPO4 leads to a significant reduction in the proliferation, migration, and invasion of glioma cells.

CONCLUSION

This study identified two glioma subtypes and constructed a prognostic signature based on DDRGs. The signature has the potential to optimize the selection of patients for immune- and chemotherapy and provided a potential therapeutic target for glioma.

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Feng L, Chen X, Sheng G, Li Y, Li Y, Zhang Y, Yao K, Wu Z, Zhang R, Kiboku T, Kawasaki A, Horimoto K, Tang Y, Sun M, Han F, Chen D. Synthesis and Bioevaluation of 3-(Arylmethylene)indole Derivatives: Discovery of a Novel ALK Modulator with Antiglioblastoma Activities. J Med Chem 2023;66:14609-14622. [PMID: 37861443 DOI: 10.1021/acs.jmedchem.3c01090] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2023]

Affiliation(s)

Lili Feng Medical Basic Research Innovation Center for Cardiovascular and Cerebrovascular Diseases, Ministry of Education, China, International Joint Laboratory for Drug Target of Critical Illnesses, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China
Xiang Chen Medical Basic Research Innovation Center for Cardiovascular and Cerebrovascular Diseases, Ministry of Education, China, International Joint Laboratory for Drug Target of Critical Illnesses, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China
Gang Sheng Medical Basic Research Innovation Center for Cardiovascular and Cerebrovascular Diseases, Ministry of Education, China, International Joint Laboratory for Drug Target of Critical Illnesses, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China
Yingchun Li Medical Basic Research Innovation Center for Cardiovascular and Cerebrovascular Diseases, Ministry of Education, China, International Joint Laboratory for Drug Target of Critical Illnesses, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China
Yingying Li Medical Basic Research Innovation Center for Cardiovascular and Cerebrovascular Diseases, Ministry of Education, China, International Joint Laboratory for Drug Target of Critical Illnesses, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China
Yixuan Zhang Gusu School, Nanjing Medical University, Suzhou Municipal Hospital, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou 215001, China
Kun Yao Laboratory of Medicinal Chemical Biology, Department of Medicinal Chemistry, College of Pharmaceutical Sciences, Soochow University, Suzhou 215006, China
Zhouyue Wu Medical Basic Research Innovation Center for Cardiovascular and Cerebrovascular Diseases, Ministry of Education, China, International Joint Laboratory for Drug Target of Critical Illnesses, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China
Rong Zhang Medical Basic Research Innovation Center for Cardiovascular and Cerebrovascular Diseases, Ministry of Education, China, International Joint Laboratory for Drug Target of Critical Illnesses, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China
Takayuki Kiboku Socium Inc., Tokyo 1350064, Japan
Atsushi Kawasaki Socium Inc., Tokyo 1350064, Japan
Katsuhisa Horimoto Socium Inc., Tokyo 1350064, Japan Artificial Intelligence Research Center, National Institute of Advanced Industrial Science and Technology, Tokyo 1350064, Japan
Yamin Tang Medical Basic Research Innovation Center for Cardiovascular and Cerebrovascular Diseases, Ministry of Education, China, International Joint Laboratory for Drug Target of Critical Illnesses, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China
Meiling Sun Department of Physiology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing 211166, China
Feng Han Medical Basic Research Innovation Center for Cardiovascular and Cerebrovascular Diseases, Ministry of Education, China, International Joint Laboratory for Drug Target of Critical Illnesses, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China Gusu School, Nanjing Medical University, Suzhou Municipal Hospital, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou 215001, China Institute of Brain Science, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing 210029, China
Dongyin Chen Medical Basic Research Innovation Center for Cardiovascular and Cerebrovascular Diseases, Ministry of Education, China, International Joint Laboratory for Drug Target of Critical Illnesses, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China

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Sun YM, Zhang YM, Shi HL, Yang S, Zhao YL, Liu HJ, Li C, Liu HL, Yang JP, Song J, Sun GZ, Yang JK. Enhancer-driven transcription of MCM8 by E2F4 promotes ATR pathway activation and glioma stem cell characteristics. Hereditas 2023;160:29. [PMID: 37349788 DOI: 10.1186/s41065-023-00292-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2023] [Accepted: 06/13/2023] [Indexed: 06/24/2023] Open

Abstract

BACKGROUND

Glioma stem cells (GSCs) are responsible for glioma recurrence and drug resistance, yet the mechanisms underlying their maintenance remains unclear. This study aimed to identify enhancer-controlled genes involved in GSCs maintenance and elucidate the mechanisms underlying their regulation.

METHODS

We analyzed RNA-seq data and H3K27ac ChIP-seq data from GSE119776 to identify differentially expressed genes and enhancers, respectively. Gene Ontology analysis was performed for functional enrichment. Transcription factors were predicted using the Toolkit for Cistrome Data Browser. Prognostic analysis and gene expression correlation was conducted using the Chinese Glioma Genome Atlas (CGGA) data. Two GSC cell lines, GSC-A172 and GSC-U138MG, were isolated from A172 and U138MG cell lines. qRT-PCR was used to detect gene transcription levels. ChIP-qPCR was used to detect H3K27ac of enhancers, and binding of E2F4 to target gene enhancers. Western blot was used to analyze protein levels of p-ATR and γH2AX. Sphere formation, limiting dilution and cell growth assays were used to analyze GSCs growth and self-renewal.

RESULTS

We found that upregulated genes in GSCs were associated with ataxia-telangiectasia-mutated-and-Rad3-related kinase (ATR) pathway activation, and that seven enhancer-controlled genes related to ATR pathway activation (LIN9, MCM8, CEP72, POLA1, DBF4, NDE1, and CDKN2C) were identified. Expression of these genes corresponded to poor prognosis in glioma patients. E2F4 was identified as a transcription factor that regulates enhancer-controlled genes related to the ATR pathway activation, with MCM8 having the highest hazard ratio among genes positively correlated with E2F4 expression. E2F4 bound to MCM8 enhancers to promote its transcription. Overexpression of MCM8 partially restored the inhibition of GSCs self-renewal, cell growth, and the ATR pathway activation caused by E2F4 knockdown.

CONCLUSION

Our study demonstrated that E2F4-mediated enhancer activation of MCM8 promotes the ATR pathway activation and GSCs characteristics. These findings offer promising targets for the development of new therapies for gliomas.

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McCornack C, Woodiwiss T, Hardi A, Yano H, Kim AH. The function of histone methylation and acetylation regulators in GBM pathophysiology. Front Oncol 2023;13:1144184. [PMID: 37205197 PMCID: PMC10185819 DOI: 10.3389/fonc.2023.1144184] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2023] [Accepted: 03/29/2023] [Indexed: 05/21/2023] Open

Jain S, Rick JW, Joshi RS, Beniwal A, Spatz J, Gill S, Chang ACC, Choudhary N, Nguyen AT, Sudhir S, Chalif EJ, Chen JS, Chandra A, Haddad AF, Wadhwa H, Shah SS, Choi S, Hayes JL, Wang L, Yagnik G, Costello JF, Diaz A, Heiland DH, Aghi MK. Single-cell RNA sequencing and spatial transcriptomics reveal cancer-associated fibroblasts in glioblastoma with protumoral effects. J Clin Invest 2023;133:e147087. [PMID: 36856115 PMCID: PMC9974099 DOI: 10.1172/jci147087] [Citation(s) in RCA: 82] [Impact Index Per Article: 41.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2021] [Accepted: 01/12/2023] [Indexed: 03/02/2023] Open

Affiliation(s)

Saket Jain Department of Neurosurgery, UCSF, San Francisco, California, USA
Jonathan W. Rick Department of Neurosurgery, UCSF, San Francisco, California, USA
Rushikesh S. Joshi Department of Neurosurgery, UCSF, San Francisco, California, USA
Angad Beniwal Department of Neurosurgery, UCSF, San Francisco, California, USA
Jordan Spatz Department of Neurosurgery, UCSF, San Francisco, California, USA
Sabraj Gill Department of Neurosurgery, UCSF, San Francisco, California, USA
Alexander Chih-Chieh Chang Department of Neurosurgery, UCSF, San Francisco, California, USA
Nikita Choudhary Department of Neurosurgery, UCSF, San Francisco, California, USA
Alan T. Nguyen Department of Neurosurgery, UCSF, San Francisco, California, USA
Sweta Sudhir Department of Neurosurgery, UCSF, San Francisco, California, USA
Eric J. Chalif Department of Neurosurgery, UCSF, San Francisco, California, USA
Jia-Shu Chen Department of Neurosurgery, UCSF, San Francisco, California, USA
Ankush Chandra Department of Neurosurgery, UCSF, San Francisco, California, USA
Alexander F. Haddad Department of Neurosurgery, UCSF, San Francisco, California, USA
Harsh Wadhwa Department of Neurosurgery, UCSF, San Francisco, California, USA
Sumedh S. Shah Department of Neurosurgery, UCSF, San Francisco, California, USA
Serah Choi Department of Neurosurgery, UCSF, San Francisco, California, USA
Josie L. Hayes Department of Neurosurgery, UCSF, San Francisco, California, USA
Lin Wang Department of Neurosurgery, UCSF, San Francisco, California, USA
Garima Yagnik Department of Neurosurgery, UCSF, San Francisco, California, USA
Joseph F. Costello Department of Neurosurgery, UCSF, San Francisco, California, USA
Aaron Diaz Department of Neurosurgery, UCSF, San Francisco, California, USA
Dieter Henrik Heiland Department of Neurosurgery, University of Freiburg, Breisgau, Germany
Manish K. Aghi Department of Neurosurgery, UCSF, San Francisco, California, USA

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Nikitin PV, Musina GR, Polozov VN, Goreiko DN, Krasnovsky VM, Werkenbark L, Kjelin M, Timashev PS. Development of Glioblastoma from Stem Cells to a Full-Fledged Tumor. Turk Patoloji Derg 2023;39:117-132. [PMID: 35876685 PMCID: PMC10518198 DOI: 10.5146/tjpath.2022.01582] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2022] [Accepted: 06/01/2022] [Indexed: 11/18/2022] Open

Li Z, Song Y, Zhang J. lncRNA PDCD4-AS1 Promotes the Progression of Glioma by Regulating miR-30b-3p/METTL7B Signaling. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2023;2023:3492480. [PMID: 37151605 PMCID: PMC10162875 DOI: 10.1155/2023/3492480] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 07/20/2022] [Accepted: 09/29/2022] [Indexed: 05/09/2023]

Hersh AM, Gaitsch H, Alomari S, Lubelski D, Tyler BM. Molecular Pathways and Genomic Landscape of Glioblastoma Stem Cells: Opportunities for Targeted Therapy. Cancers (Basel) 2022;14:3743. [PMID: 35954407 PMCID: PMC9367289 DOI: 10.3390/cancers14153743] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2022] [Revised: 07/26/2022] [Accepted: 07/27/2022] [Indexed: 02/01/2023] Open

Abstract

Glioblastoma (GBM) is an aggressive tumor of the central nervous system categorized by the World Health Organization as a Grade 4 astrocytoma. Despite treatment with surgical resection, adjuvant chemotherapy, and radiation therapy, outcomes remain poor, with a median survival of only 14-16 months. Although tumor regression is often observed initially after treatment, long-term recurrence or progression invariably occurs. Tumor growth, invasion, and recurrence is mediated by a unique population of glioblastoma stem cells (GSCs). Their high mutation rate and dysregulated transcriptional landscape augment their resistance to conventional chemotherapy and radiation therapy, explaining the poor outcomes observed in patients. Consequently, GSCs have emerged as targets of interest in new treatment paradigms. Here, we review the unique properties of GSCs, including their interactions with the hypoxic microenvironment that drives their proliferation. We discuss vital signaling pathways in GSCs that mediate stemness, self-renewal, proliferation, and invasion, including the Notch, epidermal growth factor receptor, phosphatidylinositol 3-kinase/Akt, sonic hedgehog, transforming growth factor beta, Wnt, signal transducer and activator of transcription 3, and inhibitors of differentiation pathways. We also review epigenomic changes in GSCs that influence their transcriptional state, including DNA methylation, histone methylation and acetylation, and miRNA expression. The constituent molecular components of the signaling pathways and epigenomic regulators represent potential sites for targeted therapy, and representative examples of inhibitory molecules and pharmaceuticals are discussed. Continued investigation into the molecular pathways of GSCs and candidate therapeutics is needed to discover new effective treatments for GBM and improve survival.

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Lowe SR, Kunigelis K, Vogelbaum MA. Leveraging the neurosurgical operating room for therapeutic development in NeuroOncology. Adv Drug Deliv Rev 2022;186:114337. [PMID: 35561836 DOI: 10.1016/j.addr.2022.114337] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2021] [Revised: 04/22/2022] [Accepted: 05/06/2022] [Indexed: 11/25/2022]

Zheng Y, Yue X, Fang C, Jia Z, Chen Y, Xie H, Zhao J, Yang Z, Li L, Chen Z, Bian E, Zhao B. A Novel Defined Endoplasmic Reticulum Stress-Related lncRNA Signature for Prognosis Prediction and Immune Therapy in Glioma. Front Oncol 2022;12:930923. [PMID: 35847925 PMCID: PMC9282894 DOI: 10.3389/fonc.2022.930923] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2022] [Accepted: 06/09/2022] [Indexed: 11/13/2022] Open

Affiliation(s)

Yinfei Zheng Department of Neurosurgery, The Second Affiliated Hospital of Anhui Medical University, Hefei, China Cerebral Vascular Disease Research Center, Anhui Medical University, Hefei, China
Xiaoyu Yue Department of Neurosurgery, The Second Affiliated Hospital of Anhui Medical University, Hefei, China Cerebral Vascular Disease Research Center, Anhui Medical University, Hefei, China
Cheng Fang Department of Neurosurgery, The Second Affiliated Hospital of Anhui Medical University, Hefei, China Cerebral Vascular Disease Research Center, Anhui Medical University, Hefei, China
Zhuang Jia Department of Neurosurgery, The Second Affiliated Hospital of Anhui Medical University, Hefei, China Cerebral Vascular Disease Research Center, Anhui Medical University, Hefei, China
Yuxiang Chen Department of Neurosurgery, The Second Affiliated Hospital of Anhui Medical University, Hefei, China Cerebral Vascular Disease Research Center, Anhui Medical University, Hefei, China
Han Xie Department of Neurosurgery, The Second Affiliated Hospital of Anhui Medical University, Hefei, China Cerebral Vascular Disease Research Center, Anhui Medical University, Hefei, China
Jiajia Zhao Department of Neurosurgery, The Second Affiliated Hospital of Anhui Medical University, Hefei, China Cerebral Vascular Disease Research Center, Anhui Medical University, Hefei, China
Zhihao Yang Department of Neurosurgery, The Second Affiliated Hospital of Anhui Medical University, Hefei, China Cerebral Vascular Disease Research Center, Anhui Medical University, Hefei, China
Lianxin Li Department of Neurosurgery, The Second Affiliated Hospital of Anhui Medical University, Hefei, China Cerebral Vascular Disease Research Center, Anhui Medical University, Hefei, China
Zhigang Chen Department of Neurosurgery, The Second Affiliated Hospital of Anhui Medical University, Hefei, China Cerebral Vascular Disease Research Center, Anhui Medical University, Hefei, China
Erbao Bian Department of Neurosurgery, The Second Affiliated Hospital of Anhui Medical University, Hefei, China Cerebral Vascular Disease Research Center, Anhui Medical University, Hefei, China *Correspondence: Erbao Bian, ; Bing Zhao,
Bing Zhao Department of Neurosurgery, The Second Affiliated Hospital of Anhui Medical University, Hefei, China Cerebral Vascular Disease Research Center, Anhui Medical University, Hefei, China *Correspondence: Erbao Bian, ; Bing Zhao,

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Sengupta S, Mondal M, Prasasvi KR, Mukherjee A, Magod P, Urbach S, Friedmann-Morvinski D, Marin P, Somasundaram K. Differentiated glioma cell-derived Fibromodulin activates Integrin-dependent Notch signaling in endothelial cells to promote tumor angiogenesis and growth. eLife 2022;11:78972. [PMID: 35642785 PMCID: PMC9259034 DOI: 10.7554/elife.78972] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2022] [Accepted: 05/29/2022] [Indexed: 11/13/2022] Open

Chen Z, Zhong Y, Chen J, Sun S, Liu W, Han Y, Liu X, Guo C, Li D, Hu W, Zhang P, Chen Z, Chen Z, Mou Y, Yan G, Zhu W, Yin W, Sai K. Disruption of β-catenin-mediated negative feedback reinforces cAMP-induced neuronal differentiation in glioma stem cells. Cell Death Dis 2022;13:493. [PMID: 35610201 PMCID: PMC9130142 DOI: 10.1038/s41419-022-04957-9] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Revised: 05/11/2022] [Accepted: 05/16/2022] [Indexed: 12/14/2022]

Affiliation(s)

Zhijie Chen grid.488530.20000 0004 1803 6191Department of Neurosurgery/Neuro-oncology, Sun Yat-sen University Cancer Center, Guangzhou, 510060 China ,2grid.488530.20000 0004 1803 6191State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060 China ,3grid.412558.f0000 0004 1762 1794Department of Neurosurgery, The Third Affiliated Hospital of Sun Yat-sen University Lingnan Hospital, Guangzhou, 510530 China
Yingqian Zhong grid.12981.330000 0001 2360 039XDepartment of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080 China
Jiehong Chen grid.12981.330000 0001 2360 039XDepartment of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080 China
Shuxin Sun grid.410643.4Department of Pancreas Center, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080 China
Wenfeng Liu grid.12981.330000 0001 2360 039XDepartment of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080 China
Yu Han grid.488530.20000 0004 1803 6191Department of Neurosurgery/Neuro-oncology, Sun Yat-sen University Cancer Center, Guangzhou, 510060 China ,2grid.488530.20000 0004 1803 6191State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060 China
Xincheng Liu grid.12981.330000 0001 2360 039XDepartment of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080 China
Cui Guo grid.12981.330000 0001 2360 039XDepartment of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080 China
Depei Li grid.488530.20000 0004 1803 6191Department of Neurosurgery/Neuro-oncology, Sun Yat-sen University Cancer Center, Guangzhou, 510060 China ,2grid.488530.20000 0004 1803 6191State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060 China
Wanming Hu grid.488530.20000 0004 1803 6191State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060 China ,6grid.488530.20000 0004 1803 6191Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, 510060 China
Peiyu Zhang grid.488530.20000 0004 1803 6191Department of Neurosurgery/Neuro-oncology, Sun Yat-sen University Cancer Center, Guangzhou, 510060 China ,2grid.488530.20000 0004 1803 6191State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060 China
Zhuopeng Chen grid.488530.20000 0004 1803 6191Department of Neurosurgery/Neuro-oncology, Sun Yat-sen University Cancer Center, Guangzhou, 510060 China ,2grid.488530.20000 0004 1803 6191State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060 China
Zhongping Chen grid.488530.20000 0004 1803 6191Department of Neurosurgery/Neuro-oncology, Sun Yat-sen University Cancer Center, Guangzhou, 510060 China ,2grid.488530.20000 0004 1803 6191State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060 China
Yonggao Mou grid.488530.20000 0004 1803 6191Department of Neurosurgery/Neuro-oncology, Sun Yat-sen University Cancer Center, Guangzhou, 510060 China ,2grid.488530.20000 0004 1803 6191State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060 China
Guangmei Yan grid.12981.330000 0001 2360 039XDepartment of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080 China
Wenbo Zhu grid.12981.330000 0001 2360 039XDepartment of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080 China
Wei Yin grid.12981.330000 0001 2360 039XDepartment of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080 China
Ke Sai grid.488530.20000 0004 1803 6191Department of Neurosurgery/Neuro-oncology, Sun Yat-sen University Cancer Center, Guangzhou, 510060 China ,2grid.488530.20000 0004 1803 6191State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060 China

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Chen N, Peng C, Li D. Epigenetic Underpinnings of Inflammation: A Key to Unlock the Tumor Microenvironment in Glioblastoma. Front Immunol 2022;13:869307. [PMID: 35572545 PMCID: PMC9100418 DOI: 10.3389/fimmu.2022.869307] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2022] [Accepted: 03/28/2022] [Indexed: 11/25/2022] Open

Anti-glioblastoma effects of phenolic variants of benzoylphenoxyacetamide (BPA) with high potential for blood brain barrier penetration. Sci Rep 2022;12:3384. [PMID: 35232976 PMCID: PMC8888627 DOI: 10.1038/s41598-022-07247-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2021] [Accepted: 02/14/2022] [Indexed: 12/13/2022] Open

Uribe D, Niechi I, Rackov G, Erices JI, San Martín R, Quezada C. Adapt to Persist: Glioblastoma Microenvironment and Epigenetic Regulation on Cell Plasticity. BIOLOGY 2022;11:313. [PMID: 35205179 PMCID: PMC8869716 DOI: 10.3390/biology11020313] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/30/2021] [Revised: 02/02/2022] [Accepted: 02/04/2022] [Indexed: 12/13/2022]

Abstract

Glioblastoma (GBM) is the most frequent and aggressive brain tumor, characterized by great resistance to treatments, as well as inter- and intra-tumoral heterogeneity. GBM exhibits infiltration, vascularization and hypoxia-associated necrosis, characteristics that shape a unique microenvironment in which diverse cell types are integrated. A subpopulation of cells denominated GBM stem-like cells (GSCs) exhibits multipotency and self-renewal capacity. GSCs are considered the conductors of tumor progression due to their high tumorigenic capacity, enhanced proliferation, invasion and therapeutic resistance compared to non-GSCs cells. GSCs have been classified into two molecular subtypes: proneural and mesenchymal, the latter showing a more aggressive phenotype. Tumor microenvironment and therapy can induce a proneural-to-mesenchymal transition, as a mechanism of adaptation and resistance to treatments. In addition, GSCs can transition between quiescent and proliferative substates, allowing them to persist in different niches and adapt to different stages of tumor progression. Three niches have been described for GSCs: hypoxic/necrotic, invasive and perivascular, enhancing metabolic changes and cellular interactions shaping GSCs phenotype through metabolic changes and cellular interactions that favor their stemness. The phenotypic flexibility of GSCs to adapt to each niche is modulated by dynamic epigenetic modifications. Methylases, demethylases and histone deacetylase are deregulated in GSCs, allowing them to unlock transcriptional programs that are necessary for cell survival and plasticity. In this review, we described the effects of GSCs plasticity on GBM progression, discussing the role of GSCs niches on modulating their phenotype. Finally, we described epigenetic alterations in GSCs that are important for stemness, cell fate and therapeutic resistance.

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Lopez-Bertoni H, Johnson A, Rui Y, Lal B, Sall S, Malloy M, Coulter JB, Lugo-Fagundo M, Shudir S, Khela H, Caputo C, Green JJ, Laterra J. Sox2 induces glioblastoma cell stemness and tumor propagation by repressing TET2 and deregulating 5hmC and 5mC DNA modifications. Signal Transduct Target Ther 2022;7:37. [PMID: 35136034 PMCID: PMC8826438 DOI: 10.1038/s41392-021-00857-0] [Citation(s) in RCA: 54] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2021] [Revised: 12/01/2021] [Accepted: 12/05/2021] [Indexed: 02/06/2023] Open

Affiliation(s)

Hernando Lopez-Bertoni Hugo W. Moser Research Institute at Kennedy Krieger, Baltimore, MD, USA. Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Amanda Johnson Hugo W. Moser Research Institute at Kennedy Krieger, Baltimore, MD, USA Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Yuan Rui Department of Biomedical Engineering, Institute for NanoBioTechnology, and the Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Bachchu Lal Hugo W. Moser Research Institute at Kennedy Krieger, Baltimore, MD, USA Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Sophie Sall Hugo W. Moser Research Institute at Kennedy Krieger, Baltimore, MD, USA
Maureen Malloy Bloomberg School of Public Health, Department of Environmental Health and Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
Jonathan B Coulter Bloomberg School of Public Health, Department of Environmental Health and Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD, USA The Department of Radiation Oncology and Molecular Radiation Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
Maria Lugo-Fagundo Hugo W. Moser Research Institute at Kennedy Krieger, Baltimore, MD, USA
Sweta Shudir Hugo W. Moser Research Institute at Kennedy Krieger, Baltimore, MD, USA
Harmon Khela Hugo W. Moser Research Institute at Kennedy Krieger, Baltimore, MD, USA
Christopher Caputo Hugo W. Moser Research Institute at Kennedy Krieger, Baltimore, MD, USA
Jordan J Green Department of Biomedical Engineering, Institute for NanoBioTechnology, and the Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD, USA Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA Departments of Materials Science & Engineering and Chemical & Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, USA Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
John Laterra Hugo W. Moser Research Institute at Kennedy Krieger, Baltimore, MD, USA. Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

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Zhang R, Lai W, Wang H. Quantification of Epigenetic DNA Modifications in the Subchromatin Structure Matrix Attachment Regions by Stable Isotope Dilution UHPLC-MS/MS Analysis. Anal Chem 2021;93:15567-15572. [PMID: 34783527 DOI: 10.1021/acs.analchem.1c04151] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]

Site-specific quantification of 5-carboxylcytosine in DNA by chemical conversion coupled with ligation-based PCR. CHINESE CHEM LETT 2021. [DOI: 10.1016/j.cclet.2021.05.020] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]

Vinel C, Rosser G, Guglielmi L, Constantinou M, Pomella N, Zhang X, Boot JR, Jones TA, Millner TO, Dumas AA, Rakyan V, Rees J, Thompson JL, Vuononvirta J, Nadkarni S, El Assan T, Aley N, Lin YY, Liu P, Nelander S, Sheer D, Merry CLR, Marelli-Berg F, Brandner S, Marino S. Comparative epigenetic analysis of tumour initiating cells and syngeneic EPSC-derived neural stem cells in glioblastoma. Nat Commun 2021;12:6130. [PMID: 34675201 PMCID: PMC8531305 DOI: 10.1038/s41467-021-26297-6] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2021] [Accepted: 09/23/2021] [Indexed: 12/13/2022] Open

Affiliation(s)

Claire Vinel Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University London, London, UK
Gabriel Rosser Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University London, London, UK
Loredana Guglielmi Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University London, London, UK
Myrianni Constantinou Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University London, London, UK
Nicola Pomella Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University London, London, UK
Xinyu Zhang Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University London, London, UK
James R Boot Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University London, London, UK
Tania A Jones Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University London, London, UK
Thomas O Millner Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University London, London, UK
Anaelle A Dumas Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University London, London, UK
Vardhman Rakyan Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University London, London, UK
Jeremy Rees Division of Neuropathology, The National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, Queen Square, London, UK
Jamie L Thompson Stem Cell Glycobiology Group, Biodiscovery Institute, University of Nottingham, Nottingham, UK
Juho Vuononvirta The William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University London, London, UK
Suchita Nadkarni The William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University London, London, UK
Tedani El Assan Division of Neuropathology, The National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, Queen Square, London, UK
Natasha Aley Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, Queen Square, London, UK
Yung-Yao Lin Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University London, London, UK Stem Cell Laboratory, National Bowel Research Centre, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, 2 Newark Street, London, UK
Pentao Liu Faculty of Medicine, School of Biomedical Sciences, The University of Hong Kong, Hong Kong, Hong Kong
Sven Nelander Department of Immunology Genetics and Pathology, Uppsala University, Uppsala, Sweden
Denise Sheer Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University London, London, UK
Catherine L R Merry Stem Cell Glycobiology Group, Biodiscovery Institute, University of Nottingham, Nottingham, UK
Federica Marelli-Berg The William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University London, London, UK
Sebastian Brandner Division of Neuropathology, The National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, Queen Square, London, UK Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, Queen Square, London, UK
Silvia Marino Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University London, London, UK.

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Narmontė M, Gibas P, Daniūnaitė K, Gordevičius J, Kriukienė E. Multiomics Analysis of Neuroblastoma Cells Reveals a Diversity of Malignant Transformations. Front Cell Dev Biol 2021;9:727353. [PMID: 34557494 PMCID: PMC8452964 DOI: 10.3389/fcell.2021.727353] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2021] [Accepted: 08/12/2021] [Indexed: 12/12/2022] Open

Pan T, Li X, Li Y, Tao Z, Yao H, Wu Y, Chen G, Zhang K, Zhou Y, Huang Y. USP7 inhibition induces apoptosis in glioblastoma by enhancing ubiquitination of ARF4. Cancer Cell Int 2021;21:508. [PMID: 34556124 PMCID: PMC8461901 DOI: 10.1186/s12935-021-02208-z] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2021] [Accepted: 09/11/2021] [Indexed: 12/21/2022] Open

Abstract

Background

Glioblastomas (GBMs) are grade IV central nervous system tumors characterized by a poor prognosis and a short median overall survival. Effective induction of GBM cell death is difficult because the GBM cell population is genetically unstable, resistant to chemotherapy and highly angiogenic. In recent studies, ubiquitin-specific protease 7 (USP7) is shown to scavenge ubiquitin from oncogenic protein substrates, so effective inhibition of USP7 may be a potential key treatment for GBM.

Methods

Immunohistochemistry and western blotting were used to detect the expression of USP7 in GBM tissues. In vitro apoptosis assay of USP7 inhibition was performed by western blotting, immunofluorescence, and flow cytometry. Anti-apoptotic substrates of USP7 were defined by Co-IP and TMT proteomics. Western blotting and IP were used to verify the relationship between USP7 and its substrate. In an in vivo experiment using an intracranial xenograft model in nude mice was constructed to assess the therapeutic effect of target USP7.

Results

Immunohistochemistry and western blotting confirmed that USP7 was significantly upregulated in glioblastoma samples. In in vitro experiments, inhibition of USP7 in GBM induced significant apoptosis. Co-IP and TMT proteomics identified a key anti-apoptotic substrate of USP7, ADP-ribosylation factor 4 (ARF4). Western blotting and IP confirmed that USP7 interacted directly with ARF4 and catalyzed the removal of the K48-linked polyubiquitinated chain that binded to ARF4. In addition, in vivo experiments revealed that USP7 inhibition significantly suppressed tumor growth and promoted the expression of apoptotic genes.

Conclusions

Targeted inhibition of USP7 enhances the ubiquitination of ARF4 and ultimately mediates the apoptosis of GBM cells. In a clinical sense, P5091 as a novel specific inhibitor of USP7 may be an effective approach for the treatment of GBM.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12935-021-02208-z.

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Singh O, Pratt D, Aldape K. Immune cell deconvolution of bulk DNA methylation data reveals an association with methylation class, key somatic alterations, and cell state in glial/glioneuronal tumors. Acta Neuropathol Commun 2021;9:148. [PMID: 34496929 PMCID: PMC8425010 DOI: 10.1186/s40478-021-01249-9] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2021] [Accepted: 08/23/2021] [Indexed: 02/08/2023] Open

Kucheryavenko AS, Chernomyrdin NV, Gavdush AA, Alekseeva AI, Nikitin PV, Dolganova IN, Karalkin PA, Khalansky AS, Spektor IE, Skorobogatiy M, Tuchin VV, Zaytsev KI. Terahertz dielectric spectroscopy and solid immersion microscopy of ex vivo glioma model 101.8: brain tissue heterogeneity. BIOMEDICAL OPTICS EXPRESS 2021;12:5272-5289. [PMID: 34513256 PMCID: PMC8407834 DOI: 10.1364/boe.432758] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/31/2021] [Revised: 07/15/2021] [Accepted: 07/22/2021] [Indexed: 05/23/2023]

Abballe L, Miele E. Epigenetic modulators for brain cancer stem cells: Implications for anticancer treatment. World J Stem Cells 2021;13:670-684. [PMID: 34367473 PMCID: PMC8316861 DOI: 10.4252/wjsc.v13.i7.670] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2021] [Revised: 04/26/2021] [Accepted: 06/22/2021] [Indexed: 02/06/2023] Open

Mitchell K, Troike K, Silver DJ, Lathia JD. The evolution of the cancer stem cell state in glioblastoma: emerging insights into the next generation of functional interactions. Neuro Oncol 2021;23:199-213. [PMID: 33173943 DOI: 10.1093/neuonc/noaa259] [Citation(s) in RCA: 43] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open

Chen F, Hua J, Shen H, Wang H. Effect of TWIST1 Gene on the Proliferation and Apoptosis of Human Glioma Cell Line TJ861 by Regulating Mammalian Target of Rapamycin Signaling Pathway. J BIOMATER TISS ENG 2021. [DOI: 10.1166/jbt.2021.2580] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]

Abstract To observe TWIST1 gene expression in human glioma and study the effect human glioma cell line TJ861 on the proliferation and apoptosis, and further explore its potential mechanism to provide some reference for the targeted treatment of glioma in the future. Detection of cancer tissue (Carcinoma tissue) in 55 patients with glioma by RT-PCR and Expression level of TWIST1 in normal and paracancerous tissues (Adjacent tissue), the human glioma cell line TJ861 was further divided into, Nonsense sequence group, (si-NS group), TWIST1 Inhibition group (si-TWIST1 group) and control group. The glioma cells of si-NS group and si-TWIST1 group were transfected with nonsense sequence and TWIST1 siRNA respectively by liposome transfection technology. Use CCK8 assay to test the cell proliferation ability of each group at 0, 12, 24, 36, 48 and 72 hours; 48 hours after siRNA transfection, The ability of DNA replication in each group was detected by EdU staining; Apoptosis related protein expression, in each group, was analyzed by Western blot; TUNEL staining was used to test the apoptosis rate of each group; In the end, We studied TWIST1 effect knocking down on mTOR protein expression in human glioma cells and mTOR protein expression in cancer and adjacent tissues. TWIST1 expression in glioma cells was higher, compared with normal tissues (P <0.05); After transfection of TWIST1 siRNA into human glioma cell line TJ861 in vitro, CCK8 showed glioma cells proliferation ability in si-TWIST1 group at 12, 24, 36, 48 and 72 hours was lower, compared with the control group (P <0.05); After siRNA transfection at 48 hours, the DNA replication ability of glioma cells decreased significantly (P <0.05) with EdU staining; The inhibition of TWIST1 increased Bax expression in glioma cells, and inhibited Bcl-2 expression (P < 0.05) with Western blot; TUNEL staining further confirmed that the apoptosis level of glioma cells in the si-TWIST1 group was higher, compared with the control group (P <0.05). Finally, we found that mTOR protein expression in glioma was higher, compared with adjacent tissues. in vitro experiments showed that mTOR expression in glioma cells was decreased after the inhibition of TWIST1 (P <0.05). TWIST1 expression level in glioma was increased. The inhibition of TWIST1 inhibits the proliferation of glioma by blocking the mTOR signal pathway, and promote the apoptosis of glioma. Collapse

Xu L, Chen Y, Huang Y, Sandanaraj E, Yu JS, Lin RYT, Dakle P, Ke XY, Chong YK, Koh L, Mayakonda A, Nacro K, Hill J, Huang ML, Gery S, Lim SW, Huang Z, Xu Y, Chen J, Bai L, Wang S, Wakimoto H, Yeo TT, Ang BT, Müschen M, Tang C, Tan TZ, Koeffler HP. Topography of transcriptionally active chromatin in glioblastoma. SCIENCE ADVANCES 2021;7:eabd4676. [PMID: 33931443 PMCID: PMC8087410 DOI: 10.1126/sciadv.abd4676] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/07/2020] [Accepted: 03/08/2021] [Indexed: 05/07/2023]

Affiliation(s)

Liang Xu Cancer Science Institute of Singapore, National University of Singapore, 117599, Singapore. College of Life Sciences, Zhejiang University, Hangzhou, 310058, China
Ye Chen Cancer Science Institute of Singapore, National University of Singapore, 117599, Singapore.
Yulun Huang Department of Neurosurgery, Dushu Lake Hospital Affiliated of Soochow University, Suzhou, 215124, China Department of Neurosurgery, Medical Center of Soochow University, Suzhou, 215124, China Department of Neurosurgery, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China
Edwin Sandanaraj Department of Research, National Neuroscience Institute, 308433, Singapore Singapore Institute for Clinical Sciences, Agency for Science, Technology, and Research, 117609, Singapore
John S Yu Department of Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
Ruby Yu-Tong Lin Cancer Science Institute of Singapore, National University of Singapore, 117599, Singapore
Pushkar Dakle Cancer Science Institute of Singapore, National University of Singapore, 117599, Singapore
Xin-Yu Ke Cancer Science Institute of Singapore, National University of Singapore, 117599, Singapore
Yuk Kien Chong Department of Research, National Neuroscience Institute, 308433, Singapore
Lynnette Koh Department of Research, National Neuroscience Institute, 308433, Singapore School of Biological Sciences, Nanyang Technological University, 637551, Singapore
Anand Mayakonda Cancer Science Institute of Singapore, National University of Singapore, 117599, Singapore
Kassoum Nacro Experimental Drug Development Centre, Agency for Science, Technology and Research, 138670, Singapore
Jeffrey Hill Sussex Drug Discovery Centre, School of Life Sciences, University of Sussex, Brighton BN1 9QJ, UK
Mo-Li Huang Cancer Science Institute of Singapore, National University of Singapore, 117599, Singapore School of Biology and Basic Medical Sciences, Soochow University, Suzhou, 215123, China
Sigal Gery Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
See Wee Lim Department of Research, National Neuroscience Institute, 308433, Singapore
Zhengyun Huang Cambridge-Suda Genomic Research Center, Soochow University, Suzhou, 215123, China
Ying Xu Cambridge-Suda Genomic Research Center, Soochow University, Suzhou, 215123, China
Jianxiang Chen College of Pharmacy, School of Medicine, Hangzhou Normal University, Hangzhou, 311121, China Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, 311121, China Department of Hepatology, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, 310015, China
Longchuan Bai Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI 48109, USA
Shaomeng Wang Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI 48109, USA Department of Pharmacology, University of Michigan, Ann Arbor, MI 48109, USA Department of Medicinal Chemistry, University of Michigan, Ann Arbor, MI 48109, USA
Hiroaki Wakimoto Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
Tseng Tsai Yeo National University Cancer Institute, National University Hospital, 119074, Singapore
Beng Ti Ang Department of Neurosurgery, National Neuroscience Institute, 308433, Singapore Duke-National University of Singapore Medical School, 169857, Singapore
Markus Müschen Center of Molecular and Cellular Oncology, Yale Cancer Center, Yale School of Medicine, New Haven, CT 06511, USA Department of Immunobiology, Yale University, New Haven, CT 06511, USA
Carol Tang Department of Research, National Neuroscience Institute, 308433, Singapore School of Biological Sciences, Nanyang Technological University, 637551, Singapore Cancer and Stem Cell Biology Program, Duke-National University of Singapore Medical School, 169857, Singapore
Tuan Zea Tan Cancer Science Institute of Singapore, National University of Singapore, 117599, Singapore.
H Phillip Koeffler Cancer Science Institute of Singapore, National University of Singapore, 117599, Singapore Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA National University Cancer Institute, National University Hospital, 119074, Singapore

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In silico identification of the prognostic biomarkers and therapeutic targets associated with cancer stem cell characteristics of glioma. Biosci Rep 2021;40:225916. [PMID: 32725165 PMCID: PMC7418212 DOI: 10.1042/bsr20201037] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2020] [Revised: 07/17/2020] [Accepted: 07/22/2020] [Indexed: 02/07/2023] Open

WNT-Regulated Transcriptional Enhancers and Stem Cell Plasticity. Trends Cell Biol 2021;31:525-528. [PMID: 33775538 DOI: 10.1016/j.tcb.2021.03.007] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Revised: 03/08/2021] [Accepted: 03/09/2021] [Indexed: 01/31/2023]

Li X, Nie S, Lv Z, Ma L, Song Y, Hu Z, Hu X, Liu Z, Zhou G, Dai Z, Song T, Liu J, Wang S. Overexpression of Annexin A2 promotes proliferation by forming a Glypican 1/c-Myc positive feedback loop: prognostic significance in human glioma. Cell Death Dis 2021;12:261. [PMID: 33712571 PMCID: PMC7954792 DOI: 10.1038/s41419-021-03547-5] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2020] [Revised: 02/17/2021] [Accepted: 02/19/2021] [Indexed: 12/25/2022]

Iranmanesh Y, Jiang B, Favour OC, Dou Z, Wu J, Li J, Sun C. Mitochondria's Role in the Maintenance of Cancer Stem Cells in Glioblastoma. Front Oncol 2021;11:582694. [PMID: 33692947 PMCID: PMC7937970 DOI: 10.3389/fonc.2021.582694] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2020] [Accepted: 01/08/2021] [Indexed: 12/14/2022] Open

Abstract

Glioblastoma (GBM), one of the deadliest primary brain malignancies, is characterized by a high recurrence rate due to its limited response to existing therapeutic strategies such as chemotherapy, radiation therapy, and surgery. Several mechanisms and pathways have been identified to be responsible for GBM therapeutic resistance. Glioblastoma stem cells (GSCs) are known culprits of GBM resistance to therapy. GSCs are characterized by their unique self-renewal, differentiating capacity, and proliferative potential. They form a heterogeneous population of cancer stem cells within the tumor and are further divided into different subpopulations. Their distinct molecular, genetic, dynamic, and metabolic features distinguish them from neural stem cells (NSCs) and differentiated GBM cells. Novel therapeutic strategies targeting GSCs could effectively reduce the tumor-initiating potential, hence, a thorough understanding of mechanisms involved in maintaining GSCs' stemness cannot be overemphasized. The mitochondrion, a regulator of cellular physiological processes such as autophagy, cellular respiration, reactive oxygen species (ROS) generation, apoptosis, DNA repair, and cell cycle control, has been implicated in various malignancies (for instance, breast, lung, and prostate cancer). Besides, the role of mitochondria in GBM has been extensively studied. For example, when stressors, such as irradiation and hypoxia are present, GSCs utilize specific cytoprotective mechanisms like the activation of mitochondrial stress pathways to survive the harsh environment. Proliferating GBM cells exhibit increased cytoplasmic glycolysis in comparison to terminally differentiated GBM cells and quiescent GSCs that rely more on oxidative phosphorylation (OXPHOS). Furthermore, the Warburg effect, which is characterized by increased tumor cell glycolysis and decreased mitochondrial metabolism in the presence of oxygen, has been observed in GBM. Herein, we highlight the importance of mitochondria in the maintenance of GSCs.

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Ferrer AI, Trinidad JR, Sandiford O, Etchegaray JP, Rameshwar P. Epigenetic dynamics in cancer stem cell dormancy. Cancer Metastasis Rev 2021;39:721-738. [PMID: 32394305 DOI: 10.1007/s10555-020-09882-x] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]

El Khoury LY, Fu S, Hlady RA, Wagner RT, Wang L, Eckel-Passow JE, Castle EP, Stanton ML, Thompson RH, Parker AS, Ho TH, Robertson KD. Identification of DNA methylation signatures associated with poor outcome in lower-risk Stage, Size, Grade and Necrosis (SSIGN) score clear cell renal cell cancer. Clin Epigenetics 2021;13:12. [PMID: 33461589 PMCID: PMC7814746 DOI: 10.1186/s13148-020-00998-z] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2020] [Accepted: 12/21/2020] [Indexed: 12/22/2022] Open

Affiliation(s)

Louis Y El Khoury Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, USA.,Center for Individualized Medicine, Epigenomics Program, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA
Shuang Fu Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, USA.,Center for Individualized Medicine, Epigenomics Program, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.,Hematology Laboratory, Shengjing Hospital of China Medical University, Shenyang, China
Ryan A Hlady Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, USA.,Center for Individualized Medicine, Epigenomics Program, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA
Ryan T Wagner Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, USA.,Center for Individualized Medicine, Epigenomics Program, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA
Liguo Wang Division of Biomedical Statistics and Informatics, Department of Health Science Research, Mayo Clinic, Rochester, MN, USA
Jeanette E Eckel-Passow Division of Biomedical Statistics and Informatics, Department of Health Science Research, Mayo Clinic, Rochester, MN, USA
Erik P Castle Department of Urology, Mayo Clinic, Phoenix, AZ, USA
Melissa L Stanton Department of Laboratory Medicine and Pathology, Mayo Clinic, Phoenix, AZ, USA
R Houston Thompson Department of Urology, Mayo Clinic, Rochester, MN, USA
Alexander S Parker Office of Research Affairs, University of Florida, Jacksonville, FL, USA
Thai H Ho Division of Hematology and Medical Oncology, Mayo Clinic, 13400 E. Shea Blvd, Scottsdale, AZ, 85259, USA.
Keith D Robertson Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, USA. .,Center for Individualized Medicine, Epigenomics Program, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.

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Habib A, Pease M, Kodavali CV, Amankulor N, Zinn PO. A contemporary update on glioblastoma: molecular biology, current management, and a vision towards bio-adaptable personalized care. J Neurooncol 2021;151:103-112. [PMID: 33394264 PMCID: PMC11572544 DOI: 10.1007/s11060-020-03671-w] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2020] [Accepted: 11/30/2020] [Indexed: 12/26/2022]

Chowdhury S, Ghosh S. Next Generation Sequencing and Stem Cells. Stem Cells 2021. [DOI: 10.1007/978-981-16-1638-9_8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]

Wang H, Tao Z, Feng M, Li X, Deng Z, Zhao G, Yin H, Pan T, Chen G, Feng Z, Li Y, Zhou Y. Dual PLK1 and STAT3 inhibition promotes glioblastoma cells apoptosis through MYC. Biochem Biophys Res Commun 2020;533:368-375. [PMID: 32962858 DOI: 10.1016/j.bbrc.2020.09.008] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2020] [Accepted: 09/05/2020] [Indexed: 12/27/2022]

Affiliation(s)

Hao Wang Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
Zhennan Tao Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
Ming Feng Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
Xuetao Li Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
Zhitong Deng Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
Guozheng Zhao Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
Haoran Yin Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
Tingzheng Pan Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
Guangliang Chen Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
Zibin Feng Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
Yanyan Li Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
Youxin Zhou Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.

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Valor LM, Hervás-Corpión I. The Epigenetics of Glioma Stem Cells: A Brief Overview. Front Oncol 2020;10:602378. [PMID: 33344253 PMCID: PMC7738619 DOI: 10.3389/fonc.2020.602378] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2020] [Accepted: 10/29/2020] [Indexed: 11/26/2022] Open

Leung JY, Chia K, Ong DST, Taneja R. Interweaving Tumor Heterogeneity into the Cancer Epigenetic/Metabolic Axis. Antioxid Redox Signal 2020;33:946-965. [PMID: 31841357 DOI: 10.1089/ars.2019.7942] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]

Lin S, Xu H, Zhang A, Ni Y, Xu Y, Meng T, Wang M, Lou M. Prognosis Analysis and Validation of m⁶A Signature and Tumor Immune Microenvironment in Glioma. Front Oncol 2020;10:541401. [PMID: 33123464 PMCID: PMC7571468 DOI: 10.3389/fonc.2020.541401] [Citation(s) in RCA: 58] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2020] [Accepted: 08/24/2020] [Indexed: 01/21/2023] Open

Abstract

Glioma is one of the most typical intracranial tumors, comprising about 80% of all brain malignancies. Several key molecular signatures have emerged as prognostic biomarkers, which indicate room for improvement in the current approach to glioma classification. In order to construct a more veracious prediction model and identify the potential prognosis-biomarker, we explore the differential expressed m⁶A RNA methylation regulators in 665 gliomas from TCGA-GBM and TCGA-LGG. Consensus clustering was applied to the m6A RNA methylation regulators, and two glioma subgroups were identified with a poorer prognosis and a higher grade of WHO classification in cluster 1. The further chi-squared test indicated that the immune infiltration was significantly enriched in cluster 1, indicating a close relation between m⁶A regulators and immune infiltration. In order to explore the potential biomarkers, the weighted gene co-expression network analysis (WGCNA), along with Least absolute shrinkage and selection operator (LASSO), between high/low immune infiltration and m⁶A cluster 1/2 groups were utilized for the hub genes, and four genes (TAGLN2, PDPN, TIMP1, EMP3) were identified as prognostic biomarkers. Besides, a prognostic model was constructed based on the four genes with a good prediction and applicability for the overall survival (OS) of glioma patients (the area under the curve of ROC achieved 0.80 (0.76-0.83) and 0.72 (0.68-0.76) in TCGA and Chinese Glioma Genome Atlas (CGGA), respectively). Moreover, we also found PDPN and TIMP1 were highly expressed in high-grade glioma from The Human Protein Atlas database and both of them were correlated with m6A and immune cell marker in glioma tissue samples. In conclusion, we construct a novel prognostic model which provides new insights into glioma prognosis. The PDPN and TIMP1 may serve as potential biomarkers for prognosis of glioma.

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Tao Z, Li X, Wang H, Chen G, Feng Z, Wu Y, Yin H, Zhao G, Deng Z, Zhao C, Li Y, Sun T, Zhou Y. BRD4 regulates self-renewal ability and tumorigenicity of glioma-initiating cells by enrichment in the Notch1 promoter region. Clin Transl Med 2020;10:e181. [PMID: 33135348 PMCID: PMC7533052 DOI: 10.1002/ctm2.181] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2020] [Revised: 09/09/2020] [Accepted: 09/12/2020] [Indexed: 12/24/2022] Open

Affiliation(s)

Zhennan Tao Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, P. R. China
Xuetao Li Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, P. R. China
Hao Wang Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, P. R. China
Guangliang Chen Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, P. R. China
Zibin Feng Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, P. R. China
Yue Wu Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, P. R. China
Haoran Yin Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, P. R. China
Guozheng Zhao Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, P. R. China
Zhitong Deng Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, P. R. China
Chaohui Zhao Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, P. R. China
Yanyan Li Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, P. R. China
Ting Sun Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, P. R. China
Youxin Zhou Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, P. R. China

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Ličytė J, Gibas P, Skardžiūtė K, Stankevičius V, Rukšėnaitė A, Kriukienė E. A Bisulfite-free Approach for Base-Resolution Analysis of Genomic 5-Carboxylcytosine. Cell Rep 2020;32:108155. [DOI: 10.1016/j.celrep.2020.108155] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2020] [Revised: 07/10/2020] [Accepted: 08/25/2020] [Indexed: 01/01/2023] Open

Bhargav AG, Mondal SK, Garcia CA, Green JJ, Quiñones‐Hinojosa A. Nanomedicine Revisited: Next Generation Therapies for Brain Cancer. ADVANCED THERAPEUTICS 2020. [DOI: 10.1002/adtp.202000118] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]

Han C, He Y, Chen L, Wang J, Jiao S, Xia X, Li G, Yao S. Low Expression of APOB mRNA or Its Hypermethylation Predicts Favorable Overall Survival in Patients with Low-Grade Glioma. Onco Targets Ther 2020;13:7243-7255. [PMID: 32801753 PMCID: PMC7394594 DOI: 10.2147/ott.s257794] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2020] [Accepted: 06/30/2020] [Indexed: 12/12/2022] Open