LAMB1 downregulation suppresses glioma progression by inhibiting aerobic glycolysis through regulation of the NF-κB/HK2 axis
Abstract Background Laminin subunit beta 1 (LAMB1) has regulatory functions on the proliferation, attachment, and migration of tumor cells, with increased levels linked to different cancers. Objective This study aims at investigating the effects and mechanisms of LAMB1 in glioma. Methods and materia...
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| Format: | Article |
| Language: | English |
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Springer
2025-02-01
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| Series: | Discover Oncology |
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| Online Access: | https://doi.org/10.1007/s12672-025-01818-7 |
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| author | Zhenxiang Zhao Haiying Liu Yingzi Liu Junpeng Wen Jiangwei Yuan |
| author_facet | Zhenxiang Zhao Haiying Liu Yingzi Liu Junpeng Wen Jiangwei Yuan |
| author_sort | Zhenxiang Zhao |
| collection | DOAJ |
| description | Abstract Background Laminin subunit beta 1 (LAMB1) has regulatory functions on the proliferation, attachment, and migration of tumor cells, with increased levels linked to different cancers. Objective This study aims at investigating the effects and mechanisms of LAMB1 in glioma. Methods and material Glioma cell models with LAMB1 overexpression or downregulation were constructed. Cell viability, proliferation, and invasion were evaluated. Glucose uptake and lactate production were examined, and Seahorse was used to assess the extracellular acidification rate (ECAR). The EC50 of temozolomide (TMZ) in glioma cells was tested. Western blotting was conducted to monitor the expression of HK1, HK2, PDHA, and PKM. Bioinformatic analysis was employed to investigate the downstream mechanism of LAMB1. In addition, a subcutaneous tumor model was constructed to determine the influence of LAMB1 on GBM cell growth in vivo. Results LAMB1 overexpression enhanced cell viability, proliferation, and invasion and promoted glioma cell growth. LAMB1 upregulation enhanced cellular glycolysis and repressed the sensitivity of cells to TMZ. LAMB1 activated the NF-κB pathway. Downregulation of LAMB1 or mitigating of the NF-κB pathway by Bay 11-7082 inhibited glioma cell proliferation, growth, and glycolysis and enhanced TMZ sensitivity. Conclusions LAMB1 downregulation exerted antitumor effects on glioma cells by regulating the NF-κB/HK2 axis. |
| format | Article |
| id | doaj-art-6d48ce84d5ff4208805fda9f34482576 |
| institution | Kabale University |
| issn | 2730-6011 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Springer |
| record_format | Article |
| series | Discover Oncology |
| spelling | doaj-art-6d48ce84d5ff4208805fda9f344825762025-02-09T12:43:21ZengSpringerDiscover Oncology2730-60112025-02-0116111610.1007/s12672-025-01818-7LAMB1 downregulation suppresses glioma progression by inhibiting aerobic glycolysis through regulation of the NF-κB/HK2 axisZhenxiang Zhao0Haiying Liu1Yingzi Liu2Junpeng Wen3Jiangwei Yuan4Department of Neurosurgery, The Fourth Hospital of Hebei Medical UniversityDepartment of Neurosurgery, The Fourth Hospital of Hebei Medical UniversityDepartment of Neurosurgery, The Fourth Hospital of Hebei Medical UniversityDepartment of Neurosurgery, The Fourth Hospital of Hebei Medical UniversityDepartment of Neurosurgery, The Fourth Hospital of Hebei Medical UniversityAbstract Background Laminin subunit beta 1 (LAMB1) has regulatory functions on the proliferation, attachment, and migration of tumor cells, with increased levels linked to different cancers. Objective This study aims at investigating the effects and mechanisms of LAMB1 in glioma. Methods and material Glioma cell models with LAMB1 overexpression or downregulation were constructed. Cell viability, proliferation, and invasion were evaluated. Glucose uptake and lactate production were examined, and Seahorse was used to assess the extracellular acidification rate (ECAR). The EC50 of temozolomide (TMZ) in glioma cells was tested. Western blotting was conducted to monitor the expression of HK1, HK2, PDHA, and PKM. Bioinformatic analysis was employed to investigate the downstream mechanism of LAMB1. In addition, a subcutaneous tumor model was constructed to determine the influence of LAMB1 on GBM cell growth in vivo. Results LAMB1 overexpression enhanced cell viability, proliferation, and invasion and promoted glioma cell growth. LAMB1 upregulation enhanced cellular glycolysis and repressed the sensitivity of cells to TMZ. LAMB1 activated the NF-κB pathway. Downregulation of LAMB1 or mitigating of the NF-κB pathway by Bay 11-7082 inhibited glioma cell proliferation, growth, and glycolysis and enhanced TMZ sensitivity. Conclusions LAMB1 downregulation exerted antitumor effects on glioma cells by regulating the NF-κB/HK2 axis.https://doi.org/10.1007/s12672-025-01818-7LAMB1GliomaTemozolomideResistanceGlycolysisNF-κB |
| spellingShingle | Zhenxiang Zhao Haiying Liu Yingzi Liu Junpeng Wen Jiangwei Yuan LAMB1 downregulation suppresses glioma progression by inhibiting aerobic glycolysis through regulation of the NF-κB/HK2 axis Discover Oncology LAMB1 Glioma Temozolomide Resistance Glycolysis NF-κB |
| title | LAMB1 downregulation suppresses glioma progression by inhibiting aerobic glycolysis through regulation of the NF-κB/HK2 axis |
| title_full | LAMB1 downregulation suppresses glioma progression by inhibiting aerobic glycolysis through regulation of the NF-κB/HK2 axis |
| title_fullStr | LAMB1 downregulation suppresses glioma progression by inhibiting aerobic glycolysis through regulation of the NF-κB/HK2 axis |
| title_full_unstemmed | LAMB1 downregulation suppresses glioma progression by inhibiting aerobic glycolysis through regulation of the NF-κB/HK2 axis |
| title_short | LAMB1 downregulation suppresses glioma progression by inhibiting aerobic glycolysis through regulation of the NF-κB/HK2 axis |
| title_sort | lamb1 downregulation suppresses glioma progression by inhibiting aerobic glycolysis through regulation of the nf κb hk2 axis |
| topic | LAMB1 Glioma Temozolomide Resistance Glycolysis NF-κB |
| url | https://doi.org/10.1007/s12672-025-01818-7 |
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