Restoration of Autophagy and Apoptosis in Myelodysplastic Syndromes: The Effect of Azacitidine in Disease Pathogenesis
Abstract
1. Introduction
2. Materials and Methods
2.1. The Study Group
2.2. Primary Cell Separation from MDS Patients
2.3. The MDS-L Cell Line Culture
2.4. Azacitidine Preparation
2.5. MDS-L Cell Viability After Azacitidine Treatment
2.6. RNA and Protein Extraction from the MDS-L Cells After Azacitidine Treatment
2.7. The Gene Expression Analysis Using Quantitative Real-Time PCR
2.8. The Protein Expression Analysis Using Western Blotting
2.9. The Phosphoprotein Expression Analysis Using a Multiplex ELISA Assay
2.10. Statistical Approach
3. Results
3.1. MDS Is Characterized by the Downregulation of Autophagy and Apoptosis Proteins
3.2. Azacytidine Induces Effective Cell Apoptosis in the MDS-L Cell Line
3.3. Treatment of the MDS-L Cells with Azacitidine Restored Autophagy and Apoptosis at the mRNA and Protein Levels
3.4. Azacitidine May Also Affect Phosphoproteins Related to Autophagy and Apoptosis
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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All MDS | p-Value | LR-MDS | p-Value | HR-MDS | p-Value | |
---|---|---|---|---|---|---|
AMBRA1 | −1.190165 | −1.042547 | −1.361363 | |||
ATG5 | −3.274832 | <0.001 | −2.911969 | <0.001 | −3.066072 | <0.001 |
ATG12 | −1.774992 | <0.001 | −1.126027 | −2.659288 | <0.001 | |
ATG16 | −1.483484 | −1.470517 | −1.720712 | |||
CTSB | −2.335516 | <0.02 | −2.318447 | <0.05 | −2.393512 | <0.02 |
DRAM1 | −1.916758 | <0.02 | −1.692008 | −1.984616 | <0.05 | |
LC3I | 1.612848 | 1.188060 | 1.664416 | |||
LC3II | −3.231055 | <0.001 | −2.523108 | <0.001 | −4.274320 | <0.001 |
PI3KC3 | −1.509030 | −1.478196 | −1.566015 | |||
TGM2 | 2.229709 | <0.001 | 2.162048 | <0.001 | 2.249299 | <0.001 |
UVRAG | −1.307206 | −1.042216 | −1.797932 | |||
CASP3 | −2.650488 | <0.001 | −2.542133 | <0.001 | −2.799367 | <0.001 |
CASP7 | −2.410310 | <0.001 | −2.095823 | <0.05 | −3.116006 | <0.001 |
CASP8 | −2.013422 | <0.05 | −2.109531 | <0.05 | −1.961725 | |
BCL2 | 1.647007 | <0.02 | 1.257670 | <0.02 | 2.051875 | <0.001 |
Gene/Protein | Gene Expression | Protein Expression |
---|---|---|
AMPKα | - | 1.32 * |
ATG5 | 5.58 * | 1.72 * |
BECN1 | 4.03 * | 4.44 * |
LC3II | 4.63 * | 1.72 * |
TGM2 | 1 | −1.19 * |
BCL2 | −18.54 * | −2.28 * |
Phosphoprotein | Fold Change |
---|---|
AKT | −2 * |
AKT1S1 | −1.25 |
CHK2 | 1.17 * |
c-JUN | 1.13 * |
CREB1 | −2.2 * |
EGFR | −1.62 * |
ERK1 | 1.76 * |
FAK1 | 1.1 |
GSK3a/β | −1.15 |
HSPB1 | −1.21 |
IKBA | 1.18 |
MARCKS | −1.65 * |
MEK1 | 1.2 |
MTOR | −1.2 * |
NFKB | −1.97 * |
P38 MAPK | −1.12 |
P53 | 2.3 * |
PTN11 | −1.21 |
RSK1 | −1.16 * |
SMAD3 | −1.12 |
STAT3 | −1.23 * |
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Tsekoura, G.; Agathangelidis, A.; Kontandreopoulou, C.-N.; Fasouli, E.S.; Katsantoni, E.; Pliaka, V.; Alexopoulos, L.; Katana, E.; Papaioannou, M.; Taktikou, G.; et al. Restoration of Autophagy and Apoptosis in Myelodysplastic Syndromes: The Effect of Azacitidine in Disease Pathogenesis. Curr. Issues Mol. Biol. 2025, 47, 520. https://doi.org/10.3390/cimb47070520
Tsekoura G, Agathangelidis A, Kontandreopoulou C-N, Fasouli ES, Katsantoni E, Pliaka V, Alexopoulos L, Katana E, Papaioannou M, Taktikou G, et al. Restoration of Autophagy and Apoptosis in Myelodysplastic Syndromes: The Effect of Azacitidine in Disease Pathogenesis. Current Issues in Molecular Biology. 2025; 47(7):520. https://doi.org/10.3390/cimb47070520
Chicago/Turabian StyleTsekoura, Georgia, Andreas Agathangelidis, Christina-Nefeli Kontandreopoulou, Eirini Sofia Fasouli, Eleni Katsantoni, Vaia Pliaka, Leonidas Alexopoulos, Eleni Katana, Myrto Papaioannou, Georgia Taktikou, and et al. 2025. "Restoration of Autophagy and Apoptosis in Myelodysplastic Syndromes: The Effect of Azacitidine in Disease Pathogenesis" Current Issues in Molecular Biology 47, no. 7: 520. https://doi.org/10.3390/cimb47070520
APA StyleTsekoura, G., Agathangelidis, A., Kontandreopoulou, C.-N., Fasouli, E. S., Katsantoni, E., Pliaka, V., Alexopoulos, L., Katana, E., Papaioannou, M., Taktikou, G., Strataki, M. E., Taliouraki, A., Mantzourani, M., Viniou, N.-A., Diamantopoulos, P. T., & Kollia, P. (2025). Restoration of Autophagy and Apoptosis in Myelodysplastic Syndromes: The Effect of Azacitidine in Disease Pathogenesis. Current Issues in Molecular Biology, 47(7), 520. https://doi.org/10.3390/cimb47070520