Cereblon upregulation overcomes thalidomide resistance in multiple myeloma through mitochondrial functional reprogramming.
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| Natura: | Artículo científico |
| Lingua: | en |
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BMB reports
2026
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| _version_ | 1868266154886168578 |
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| author | Marquez, Jubert Park, Nammi Choi, Jae Hyeog Garcia, Maria Victoria Faith Flores, Jessa Nyamaa, Bayalagmaa Seol, Jung Eun Kim, Hyoung Kyu Shin, Myung Geun Park, Sae Gwang Han, Jin |
| author_facet | Marquez, Jubert Park, Nammi Choi, Jae Hyeog Garcia, Maria Victoria Faith Flores, Jessa Nyamaa, Bayalagmaa Seol, Jung Eun Kim, Hyoung Kyu Shin, Myung Geun Park, Sae Gwang Han, Jin Marquez, Jubert Park, Nammi Choi, Jae Hyeog Garcia, Maria Victoria Faith Flores, Jessa Nyamaa, Bayalagmaa Seol, Jung Eun Kim, Hyoung Kyu Shin, Myung Geun Park, Sae Gwang Han, Jin |
| collection | PubMed - marine biology |
| contents | Cereblon upregulation overcomes thalidomide resistance in multiple myeloma through mitochondrial functional reprogramming. Marquez, Jubert Park, Nammi Choi, Jae Hyeog Garcia, Maria Victoria Faith Flores, Jessa Nyamaa, Bayalagmaa Seol, Jung Eun Kim, Hyoung Kyu Shin, Myung Geun Park, Sae Gwang Han, Jin Multiple Myeloma Humans Animals Thalidomide Mitochondria Ubiquitin-Protein Ligases Mice Drug Resistance, Neoplasm Cell Line, Tumor Adaptor Proteins, Signal Transducing Up-Regulation Mice, Inbred BALB C Mice, Nude Xenograft Model Antitumor Assays Cell Survival Membrane Potential, Mitochondrial Signal Transduction Reactive Oxygen Species Patients with multiple myeloma develop resistance to thalidomide during therapy, and the mechanisms to counteract thalidomide resistance remain elusive. Here, we explored the interaction between cereblon and mitochondrial function to mitigate thalidomide resistance in multiple myeloma. Measurements of cell viability, ATP production, mitochondrial membrane potential, mitochondrial ROS, and protein expression via western blotting were conducted in vitro using KSM20 and KMS26 cells to assess the impact of thalidomide on multiple myeloma. An in vivo analysis using xenografted multiple myeloma cells in BALB/c nude mice revealed that KMS20 cells were resistant to thalidomide, whereas KMS26 cells were sensitive. Overexpression of CRBN in a KMS20 xenograft model reversed its resistance to thalidomide, reduced tumor growth, and significantly extended the survival rate of the mice. Overexpression of CRBN in thalidomide-resistant KMS20 cells during thalidomide treatment led to effective cell death through the modulation of mitochondrial function and protein expression, mediated by AMPKα1 signaling. Conversely, both genetic and pharmacological knockdowns of CRBN rendered KMS26 cells resistant to thalidomide, indicating that CRBN level modulation directly influences mitochondrial functions. These findings propose that targeting cereblon offers a promising strategy in overcoming thalidomide resistance in multiple myeloma through mitochondrial reprogramming. [BMB Reports 2026; 59(3): 193-200]. |
| format | Artículo científico |
| id | pubmed_40916643 |
| institution | PubMed |
| language | en |
| publishDate | 2026 |
| publisher | BMB reports |
| record_format | pubmed |
| spellingShingle | Cereblon upregulation overcomes thalidomide resistance in multiple myeloma through mitochondrial functional reprogramming. Marquez, Jubert Park, Nammi Choi, Jae Hyeog Garcia, Maria Victoria Faith Flores, Jessa Nyamaa, Bayalagmaa Seol, Jung Eun Kim, Hyoung Kyu Shin, Myung Geun Park, Sae Gwang Han, Jin Multiple Myeloma Humans Animals Thalidomide Mitochondria Ubiquitin-Protein Ligases Mice Drug Resistance, Neoplasm Cell Line, Tumor Adaptor Proteins, Signal Transducing Up-Regulation Mice, Inbred BALB C Mice, Nude Xenograft Model Antitumor Assays Cell Survival Membrane Potential, Mitochondrial Signal Transduction Reactive Oxygen Species Cereblon upregulation overcomes thalidomide resistance in multiple myeloma through mitochondrial functional reprogramming. Marquez, Jubert Park, Nammi Choi, Jae Hyeog Garcia, Maria Victoria Faith Flores, Jessa Nyamaa, Bayalagmaa Seol, Jung Eun Kim, Hyoung Kyu Shin, Myung Geun Park, Sae Gwang Han, Jin Multiple Myeloma Humans Animals Thalidomide Mitochondria Ubiquitin-Protein Ligases Mice Drug Resistance, Neoplasm Cell Line, Tumor Adaptor Proteins, Signal Transducing Up-Regulation Mice, Inbred BALB C Mice, Nude Xenograft Model Antitumor Assays Cell Survival Membrane Potential, Mitochondrial Signal Transduction Reactive Oxygen Species Patients with multiple myeloma develop resistance to thalidomide during therapy, and the mechanisms to counteract thalidomide resistance remain elusive. Here, we explored the interaction between cereblon and mitochondrial function to mitigate thalidomide resistance in multiple myeloma. Measurements of cell viability, ATP production, mitochondrial membrane potential, mitochondrial ROS, and protein expression via western blotting were conducted in vitro using KSM20 and KMS26 cells to assess the impact of thalidomide on multiple myeloma. An in vivo analysis using xenografted multiple myeloma cells in BALB/c nude mice revealed that KMS20 cells were resistant to thalidomide, whereas KMS26 cells were sensitive. Overexpression of CRBN in a KMS20 xenograft model reversed its resistance to thalidomide, reduced tumor growth, and significantly extended the survival rate of the mice. Overexpression of CRBN in thalidomide-resistant KMS20 cells during thalidomide treatment led to effective cell death through the modulation of mitochondrial function and protein expression, mediated by AMPKα1 signaling. Conversely, both genetic and pharmacological knockdowns of CRBN rendered KMS26 cells resistant to thalidomide, indicating that CRBN level modulation directly influences mitochondrial functions. These findings propose that targeting cereblon offers a promising strategy in overcoming thalidomide resistance in multiple myeloma through mitochondrial reprogramming. [BMB Reports 2026; 59(3): 193-200]. |
| title | Cereblon upregulation overcomes thalidomide resistance in multiple myeloma through mitochondrial functional reprogramming. |
| topic | Multiple Myeloma Humans Animals Thalidomide Mitochondria Ubiquitin-Protein Ligases Mice Drug Resistance, Neoplasm Cell Line, Tumor Adaptor Proteins, Signal Transducing Up-Regulation Mice, Inbred BALB C Mice, Nude Xenograft Model Antitumor Assays Cell Survival Membrane Potential, Mitochondrial Signal Transduction Reactive Oxygen Species |
| url | https://pubmed.ncbi.nlm.nih.gov/40916643/ |