Role of Rac1 in p53-Related Proliferation and Drug Sensitivity in Multiple Myeloma †
Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Cell Lines
2.2. Patients
2.3. Reagents
2.4. Expression of Wild-Type p53 Using Tet-On System
2.5. Gene Knockdown
2.6. Isolation of Nucleic Acids and RNA Expression Analysis Using PCR
2.7. Western Blotting Analysis
2.8. Flow Cytometry Analysis
2.9. RNA Sequencing
2.10. Statistical Analysis
3. Results
3.1. Gene Ontology Analysis of p53, p21, and Mdm2 Protein Expression and Proliferation in Tet-On p53 HMCLs
3.2. Expression of RAC1 in Multiple Myeloma Patient Samples and HMCLs
3.3. MM Cell Proliferation and Apoptosis After Treatment with 1A-116
3.4. Cell Survival in RAC1 Knockdown MM Cells and Transcriptome Analysis
3.5. Effect of Rac1 on Sensitivity Against Cereblon Modulators and Transcriptome Analysis
3.6. Alteration of Gene Expression Profile by Rac1 Inhibition
3.7. Prognosis of Patients with MM
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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RAC1 High (n = 57) | RAC1 Low (n = 57) | p-Value | |
---|---|---|---|
Age | 71 (41–87) | 71 (42–86) | 1.00 |
Sex | 0.70 | ||
Male | 24 (42.1%) | 21 (36.8%) | |
Female | 33 (57.9%) | 36 (63.2%) | |
ALB | 3.45 (2.0–4.8) | 3.60 (2.2–4.6) | 0.73 |
Hb | 10.65 (5.9–15.7) | 10.10 (6.3–14.6) | 0.17 |
LDH | 177 (92–353) | 169 (99–497) | 0.78 |
β2MG | 3.8 (1.4–27.0) | 4.4 (1.8–29.1) | 0.21 |
IgH | 0.43 | ||
IgG | 37 (66.1%) | 32 (56.1%) | |
IgA | 12 (21.4%) | 16 (28.1%) | |
IgD | 0 (0.0%) | 2 (3.5%) | |
IgE | 0 (0.0%) | 1 (1.8%) | |
BJ | 7 (12.5%) | 5 (8.8%) | |
Non | 0 (0.0%) | 1 (1.8%) | |
IgL | 0.16 | ||
κ | 35 (62.5%) | 27 (47.4%) | |
λ | 21 (37.5%) | 29 (50.9%) | |
Non | 0 (0.0%) | 1 (1.8%) | |
Cytogenetic Risk | 0.28 | ||
Standard | 43 (79.6%) | 40 (70.2%) | |
High | 11 (20.4%) | 17 (29.8%) | |
ISS | 0.59 | ||
1 | 15 (27.3%) | 11 (21.2%) | |
2 | 24 (43.6%) | 21 (40.4%) | |
3 | 16 (29.1%) | 20 (38.5%) | |
R-ISS | 0.49 | ||
1 | 12 (22.6%) | 7 (13.2%) | |
2 | 36 (67.9%) | 40 (75.5%) | |
3 | 5 (9.4%) | 6 (11.3%) | |
ASCT | 0.18 | ||
Yes | 11 (22.9%) | 18 (37.5%) | |
No | 37 (77.1%) | 30 (62.5%) |
OS Hazard Ratio (95% CI) | p-Value | PFS Hazard Ratio (95% CI) | p-Value | ||
---|---|---|---|---|---|
R-ISS | ≥2 | 1.751 | 0.30 | 1.628 | 0.25 |
(0.608–5.039) | (0.710–3.730) | ||||
ASCT | Yes | 0.409 | 0.04 | 0.405 | 0.01 |
(0.175–0.954) | (0.201–0.814) | ||||
RAC1 mRNA | High | 2.211 | 0.02 | 1.287 | 0.37 |
(1.123–4.350) | (0.738–2.243) |
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Matsumura, I.; Oda, T.; Kasamatsu, T.; Murakami, Y.; Ishihara, R.; Ohmori, A.; Matsumoto, A.; Gotoh, N.; Kobayashi, N.; Miyazawa, Y.; et al. Role of Rac1 in p53-Related Proliferation and Drug Sensitivity in Multiple Myeloma. Cancers 2025, 17, 461. https://doi.org/10.3390/cancers17030461
Matsumura I, Oda T, Kasamatsu T, Murakami Y, Ishihara R, Ohmori A, Matsumoto A, Gotoh N, Kobayashi N, Miyazawa Y, et al. Role of Rac1 in p53-Related Proliferation and Drug Sensitivity in Multiple Myeloma. Cancers. 2025; 17(3):461. https://doi.org/10.3390/cancers17030461
Chicago/Turabian StyleMatsumura, Ikuko, Tsukasa Oda, Tetsuhiro Kasamatsu, Yuki Murakami, Rei Ishihara, Ayane Ohmori, Akira Matsumoto, Nanami Gotoh, Nobuhiko Kobayashi, Yuri Miyazawa, and et al. 2025. "Role of Rac1 in p53-Related Proliferation and Drug Sensitivity in Multiple Myeloma" Cancers 17, no. 3: 461. https://doi.org/10.3390/cancers17030461
APA StyleMatsumura, I., Oda, T., Kasamatsu, T., Murakami, Y., Ishihara, R., Ohmori, A., Matsumoto, A., Gotoh, N., Kobayashi, N., Miyazawa, Y., Ogawa, Y., Yokohama, A., Sasaki, N., Saitoh, T., & Handa, H. (2025). Role of Rac1 in p53-Related Proliferation and Drug Sensitivity in Multiple Myeloma. Cancers, 17(3), 461. https://doi.org/10.3390/cancers17030461