Chromobox protein homolog 7 suppresses the stem-like phenotype of glioblastoma cells by regulating the myosin heavy chain 9-NF-κB signaling pathway

Abstract Cancer stem cells (CSCs) are significant factors in the treatment resistance and recurrence of glioblastoma. Chromobox protein homolog 7 (CBX7) can inhibit the progression of various tumors, but its impact on the stem cell-like properties of glioblastoma cells remains unclear. Clinically, l...

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Main Authors: Kaixiang Ni, Yuankun Liu, Pinggang DI, Lu Wang, Hui Huang, R. M. Damian Holsinger, Karrie Mei-Yee Kiang, Jiantong Jiao
Format: Article
Language:English
Published: Nature Publishing Group 2025-02-01
Series:Cell Death Discovery
Online Access:https://doi.org/10.1038/s41420-025-02362-7
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author Kaixiang Ni
Yuankun Liu
Pinggang DI
Lu Wang
Hui Huang
R. M. Damian Holsinger
Karrie Mei-Yee Kiang
Jiantong Jiao
author_facet Kaixiang Ni
Yuankun Liu
Pinggang DI
Lu Wang
Hui Huang
R. M. Damian Holsinger
Karrie Mei-Yee Kiang
Jiantong Jiao
author_sort Kaixiang Ni
collection DOAJ
description Abstract Cancer stem cells (CSCs) are significant factors in the treatment resistance and recurrence of glioblastoma. Chromobox protein homolog 7 (CBX7) can inhibit the progression of various tumors, but its impact on the stem cell-like properties of glioblastoma cells remains unclear. Clinically, low levels of CBX7 are associated with poor prognosis and increased distant metastasis in glioblastoma patients, and this low expression is caused by methylation of the CBX7 promoter. Our current research indicates that CBX7 plays a key role in suppressing the stem-like phenotype of glioblastoma. In this study, through bioinformatics analysis, we found that CBX7 is the most significantly downregulated member of the CBX family in glioblastoma and is closely associated with the stem-like phenotype of glioblastoma cells. We show that CBX7 promotes the degradation of myosin heavy chain 9 (MYH9) protein through the ubiquitin-proteasome pathway via the polycomb repressive complex 1 (PRC1) and suppresses the stem-like phenotype of glioblastoma cells by inhibiting the nuclear factor kappa-B (NF-κB) signaling pathway. Furthermore, overexpression of MYH9 in glioblastoma cells reverses the inhibitory effects of CBX7 on migration, proliferation, invasion, and stemness of glioblastoma cells. In summary, CBX7 acts as a tumor suppressor by inhibiting the stem cell-like characteristics of glioblastoma. The CBX7-MYH9-NF-κB signaling axis may serve as a potential therapeutic target for glioblastoma.
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spelling doaj-art-370832cfe8b24ceeae76745ef21806d72025-08-20T02:15:15ZengNature Publishing GroupCell Death Discovery2058-77162025-02-0111111610.1038/s41420-025-02362-7Chromobox protein homolog 7 suppresses the stem-like phenotype of glioblastoma cells by regulating the myosin heavy chain 9-NF-κB signaling pathwayKaixiang Ni0Yuankun Liu1Pinggang DI2Lu Wang3Hui Huang4R. M. Damian Holsinger5Karrie Mei-Yee Kiang6Jiantong Jiao7The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical UniversityThe Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical UniversityDepartment of Emergency, Wulian County People’s HospitalDepartment of Pathology, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi People’s Hospital, Nanjing Medical UniversityThe Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical UniversityLaboratory of Molecular Neuroscience and Dementia, School of Medical Sciences, Faculty of Medicine and Health, The University of SydneyDivision of Neurosurgery, Department of Surgery, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong KongThe Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical UniversityAbstract Cancer stem cells (CSCs) are significant factors in the treatment resistance and recurrence of glioblastoma. Chromobox protein homolog 7 (CBX7) can inhibit the progression of various tumors, but its impact on the stem cell-like properties of glioblastoma cells remains unclear. Clinically, low levels of CBX7 are associated with poor prognosis and increased distant metastasis in glioblastoma patients, and this low expression is caused by methylation of the CBX7 promoter. Our current research indicates that CBX7 plays a key role in suppressing the stem-like phenotype of glioblastoma. In this study, through bioinformatics analysis, we found that CBX7 is the most significantly downregulated member of the CBX family in glioblastoma and is closely associated with the stem-like phenotype of glioblastoma cells. We show that CBX7 promotes the degradation of myosin heavy chain 9 (MYH9) protein through the ubiquitin-proteasome pathway via the polycomb repressive complex 1 (PRC1) and suppresses the stem-like phenotype of glioblastoma cells by inhibiting the nuclear factor kappa-B (NF-κB) signaling pathway. Furthermore, overexpression of MYH9 in glioblastoma cells reverses the inhibitory effects of CBX7 on migration, proliferation, invasion, and stemness of glioblastoma cells. In summary, CBX7 acts as a tumor suppressor by inhibiting the stem cell-like characteristics of glioblastoma. The CBX7-MYH9-NF-κB signaling axis may serve as a potential therapeutic target for glioblastoma.https://doi.org/10.1038/s41420-025-02362-7
spellingShingle Kaixiang Ni
Yuankun Liu
Pinggang DI
Lu Wang
Hui Huang
R. M. Damian Holsinger
Karrie Mei-Yee Kiang
Jiantong Jiao
Chromobox protein homolog 7 suppresses the stem-like phenotype of glioblastoma cells by regulating the myosin heavy chain 9-NF-κB signaling pathway
Cell Death Discovery
title Chromobox protein homolog 7 suppresses the stem-like phenotype of glioblastoma cells by regulating the myosin heavy chain 9-NF-κB signaling pathway
title_full Chromobox protein homolog 7 suppresses the stem-like phenotype of glioblastoma cells by regulating the myosin heavy chain 9-NF-κB signaling pathway
title_fullStr Chromobox protein homolog 7 suppresses the stem-like phenotype of glioblastoma cells by regulating the myosin heavy chain 9-NF-κB signaling pathway
title_full_unstemmed Chromobox protein homolog 7 suppresses the stem-like phenotype of glioblastoma cells by regulating the myosin heavy chain 9-NF-κB signaling pathway
title_short Chromobox protein homolog 7 suppresses the stem-like phenotype of glioblastoma cells by regulating the myosin heavy chain 9-NF-κB signaling pathway
title_sort chromobox protein homolog 7 suppresses the stem like phenotype of glioblastoma cells by regulating the myosin heavy chain 9 nf κb signaling pathway
url https://doi.org/10.1038/s41420-025-02362-7
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