MYC Causes Multiple Myeloma Progression via Attenuating TP53-Induced MicroRNA-34 Expression
Abstract
:1. Introduction
2. Materials and Methods
2.1. Cell Lines
2.2. Patients
2.3. Treatment with MDM2 Inhibitor Nutlin-3
2.4. p53 Overexpression Using Tet-On System
2.5. Treatment with Myc Inhibitor
2.6. MYC Activation in MYC-ER Cell Lines
2.7. Isolation of Nucleic Acids
2.8. Real-Time PCR
2.9. Western Blot
2.10. Apoptosis Analysis
2.11. Statistical Analysis
3. Results
3.1. miR-34 Family and TP53 mRNA Expressions and Their Correlations in the Patients
3.2. p53 Protein Accumulation and p53 Overexpression Upregulated Primary and Mature miR-34 in Human Multiple Myeloma Cell Lines (HMCLs)
3.3. MYC mRNA Expression in Patients
3.4. Myc Inhibitor Alone Did Not Change miR-34 Family Expression in Most HMCLs
3.5. WT p53 Accumulation and Myc Inhibition Synergistically Upregulated miR-34 Expression
3.6. Forced MYC Activation Repressed p53-Mediated miR-34 Expression in MYC-ER Cell Lines
3.7. MM Cell Proliferation and Apoptosis after Co-Treatment with Nutlin-3 and Myc Inhibitor
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Group | MGUS | MM | |
---|---|---|---|
n | 64 | 109 | |
age | 71 (38–88) | 69.5 (44–88) | |
Gender (%) | F | 37 (58.7) | 53 (49.1) |
M | 26 (41.3) | 55 (50.9) | |
IgH (%) | BJ | 2 (3.5) | 19 (17.6) |
IgG | 40 (70.2) | 63 (58.3) | |
IgA | 11 (19.3) | 22 (20.4) | |
IgD | 0 (0.0) | 2 (1.9) | |
IgM | 2 (3.5) | 0 (0.0) | |
unknown | 2 (3.5) | 2 (1.9) | |
IgL (%) | κ | 31 (54.4) | 60 (55.6) |
λ | 24 (42.1) | 46 (42.6) | |
unknown | 2 (3.5) | 2 (1.9) | |
ISS (%) | 1 | NA | 22 (21.0) |
2 | NA | 45 (42.9) | |
3 | NA | 38 (36.2) | |
R.ISS (%) | 1 | NA | 12 (12.1) |
2 | NA | 72 (72.7) | |
3 | NA | 15 (15.2) | |
Cytogenetics.Risk (%) | High | NA | 35 (34.3) |
Standard | NA | 67 (65.7) | |
Cytogenetics.Karyotype (%) | del 17p | NA | 12 (12.5) |
t (11; 14) | NA | 21 (21.9) | |
t (14; 16) | NA | 2 (2.1) | |
t (4; 14) | NA | 16 (16.7) | |
trisomy11 | NA | 18 (18.8) | |
NP | NA | 27 (28.1) |
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Murakami, Y.; Kimura-Masuda, K.; Oda, T.; Matsumura, I.; Masuda, Y.; Ishihara, R.; Watanabe, S.; Kuroda, Y.; Kasamatsu, T.; Gotoh, N.; et al. MYC Causes Multiple Myeloma Progression via Attenuating TP53-Induced MicroRNA-34 Expression. Genes 2023, 14, 100. https://doi.org/10.3390/genes14010100
Murakami Y, Kimura-Masuda K, Oda T, Matsumura I, Masuda Y, Ishihara R, Watanabe S, Kuroda Y, Kasamatsu T, Gotoh N, et al. MYC Causes Multiple Myeloma Progression via Attenuating TP53-Induced MicroRNA-34 Expression. Genes. 2023; 14(1):100. https://doi.org/10.3390/genes14010100
Chicago/Turabian StyleMurakami, Yuki, Kei Kimura-Masuda, Tsukasa Oda, Ikuko Matsumura, Yuta Masuda, Rei Ishihara, Saki Watanabe, Yuko Kuroda, Tetsuhiro Kasamatsu, Nanami Gotoh, and et al. 2023. "MYC Causes Multiple Myeloma Progression via Attenuating TP53-Induced MicroRNA-34 Expression" Genes 14, no. 1: 100. https://doi.org/10.3390/genes14010100
APA StyleMurakami, Y., Kimura-Masuda, K., Oda, T., Matsumura, I., Masuda, Y., Ishihara, R., Watanabe, S., Kuroda, Y., Kasamatsu, T., Gotoh, N., Takei, H., Kobayashi, N., Saitoh, T., Murakami, H., & Handa, H. (2023). MYC Causes Multiple Myeloma Progression via Attenuating TP53-Induced MicroRNA-34 Expression. Genes, 14(1), 100. https://doi.org/10.3390/genes14010100