Proteasome 26S Subunit, non-ATPase 3 (PSMD3) Regulates Breast Cancer by Stabilizing HER2 from Degradation
Abstract
:1. Introduction
2. Results
2.1. PSMD3 Expression Is Coupled with HER2 Expression
2.2. PSMD3 Expression Is Associated with HER2+ Patients, According to the Oncomine and TCGA Databases
2.3. Direct Interaction Between PSMD3 and HER2 in HER2+ BC Cell Lines
2.4. PSMD3 Stabilizes HER2 at Protein Level
2.5. PSMD3 Silencing Inhibits Cell Proliferation and Induces Cellular Apoptosis
2.6. Silencing of PSMD3 Enhanced Ubiquitination and Lysosomal Process in Correlation with Decrease HER2 Level
2.7. PSMD3 Is Dependent on Proteasome
2.8. Correlation of PSMD3 Expression with Clinicopathological Features in BC
3. Discussions
4. Materials and Methods
4.1. Clinical Patient Samples
4.2. Cell lines and Cell Culture
4.3. RNA Isolation, Conventional PCR, and Real-Time Quantitative PCR
4.4. Oncomine, TCGA and Kaplan-Meier Plotter Data Set Analysis
4.5. Immunohistochemistry (IHC) Staining and Scoring System
4.6. Immunoprecipitation (IP)
4.7. Immunoblotting
4.8. Construction of Plasmids
4.9. Immunofluorescence (IF) Staining and Confocal Microscopy
4.10. Cell Proliferation and Colony Formation Assays
4.11. Apoptotic Assay
4.12. Ubiquitination Assay
4.13. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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Parameters | Categories | PSMD3 Low mRNA(n) | PSMD3 High mRNA(n) | p-Value |
---|---|---|---|---|
HER2 status | Positive | 52 | 133 | 0.000 *** |
Negative | 164 | 163 | ||
NA = 700 | ||||
ER status | Positive | 151 | 205 | 0.874 |
Negative | 65 | 91 | ||
†NA = 700 | ||||
TNBC | TNBC | 49 | 49 | 0.082 |
Non-TNBC | 167 | 247 | ||
†NA = 700 | ||||
Tumor size | T1 | 173 | 135 | 0.000 *** |
T2 | 340 | 366 | ||
T3 | 75 | 75 | ||
T4 | 6 | 30 | ||
†NA = 12 | ||||
Node | N0 | 288 | 273 | 0.787 |
N1 | 203 | 213 | ||
N2 | 63 | 69 | ||
N3 | 53 | 50 | ||
Stage | I | 120 | 89 | 0.036 * |
II | 343 | 348 | ||
III | 130 | 148 | ||
IV | 13 | 21 |
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Fararjeh, A.S.; Chen, L.-C.; Ho, Y.-S.; Cheng, T.-C.; Liu, Y.-R.; Chang, H.-L.; Chang, H.-W.; Wu, C.-H.; Tu, S.-H. Proteasome 26S Subunit, non-ATPase 3 (PSMD3) Regulates Breast Cancer by Stabilizing HER2 from Degradation. Cancers 2019, 11, 527. https://doi.org/10.3390/cancers11040527
Fararjeh AS, Chen L-C, Ho Y-S, Cheng T-C, Liu Y-R, Chang H-L, Chang H-W, Wu C-H, Tu S-H. Proteasome 26S Subunit, non-ATPase 3 (PSMD3) Regulates Breast Cancer by Stabilizing HER2 from Degradation. Cancers. 2019; 11(4):527. https://doi.org/10.3390/cancers11040527
Chicago/Turabian StyleFararjeh, Abdulfattah Salah, Li-Ching Chen, Yuan-Soon Ho, Tzu-Chun Cheng, Yun-Ru Liu, Hang-Lung Chang, Hui-Wen Chang, Chih-Hsiung Wu, and Shih-Hsin Tu. 2019. "Proteasome 26S Subunit, non-ATPase 3 (PSMD3) Regulates Breast Cancer by Stabilizing HER2 from Degradation" Cancers 11, no. 4: 527. https://doi.org/10.3390/cancers11040527