Dysregulated miRNA Expression and Androgen Receptor Loss in Racially Distinct Triple-Negative Breast Cancer
Abstract
:1. Introduction
2. Results
2.1. Loss of AR Associated with AA TNBCs
2.2. Differences in AR Gene Methylation Status, Mutations, and Copy Number Alterations (CNAs) Between AA and EA QNBC
2.3. Differentially Expressed miRNAs Underlie Racial Disparity
2.4. Six miRNAs That Discriminated AA QNBC from EA QNBC
2.5. Prognostic Significance of miRNA in Racially Distinct Tumors
2.6. Functional Enrichment Pathway and Protein–Protein Interaction (PPI) Analysis
3. Discussion
4. Materials and Methods
4.1. Study Design
4.2. Study Cohort
4.3. Immunohistochemistry (IHC)
4.4. AR Gene Methylation Status, Mutations, and Copy Number Alterations Analysis (TCGA Database)
4.5. RNA Isolation
4.6. MiRNA Expression Analysis
4.7. MiRNA Targets Selection
4.8. Biological Function and Pathway Analysis
4.9. Interaction of miRNA–mRNA Pairings
4.10. Statistical Analysis
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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Log2FC | p-Value | |
---|---|---|
hsa-miR-1185-5p | 1.012128 | 0.037838 |
hsa-miR-1305 | −0.999874 | 0.007647 |
hsa-miR-3161 | −0.570746 | 0.038412 |
hsa-miR-3690 | 0.216897 | 0.047954 |
hsa-miR-494-3p | −0.943088 | 0.024355 |
hsa-miR-509-3-5p | 0.265410 | 0.020465 |
hsa-miR-619-3p | 0.259912 | 0.030826 |
hsa-miR-628-3p | 0.455397 | 0.001020 |
hsa-miR-873-5p | 0.364058 | 0.024755 |
hsa-miR-877-5p | −1.080339 | 0.0168850 |
miRNA | Evidence | p-Value | Targets |
---|---|---|---|
hsa-miR-1258 | Experimental (any) | 0.038 | RB1, RLN1 |
hsa-miR-184 | Experimental (any) | 0.045 | AKT1, CARM1 |
hsa-miR-429 | Experimental (any) | 0.006 | EP300, JUN, NCOA2, PTEN, SP1 |
hsa-miR-494-3p | Experimental (any) | 8.72 × 10−4 | AKT1, BAG1, CCND1, PTEN, RB1, RHOB |
hsa-miR-520c-3p | Experimental (strong) | 0.025 | SIRT1, STAT3 |
hsa-miR-628-3p | Experimental (any) | 0.031 | CREBBP, RUNX2 |
hsa-miR-95-3p | Experimental (strong) | 0.007 | CCND1, CDKN1A |
miRNAs | Discovery Set | Validation Set |
---|---|---|
hsa-miR-1185-5p * | Up-regulated | Up-regulated |
hsa-miR-1200 | Up-regulated | Down-regulated |
hsa-miR-1244 | Up-regulated | Down-regulated |
hsa-miR-1258 ** | Up-regulated | Down-regulated |
hsa-miR-1281 | Up-regulated | Up-regulated |
hsa-miR-1293 | Up-regulated | Down-regulated |
hsa-miR-1305 * | Down-regulated | Down-regulated |
hsa-miR-2116-5p | Down-regulated | Down-regulated |
hsa-miR-218-5p | Down-regulated | Up-regulated |
hsa-miR-608 | Up-regulated | Down-regulated |
hsa-miR-613 | Up-regulated | Down-regulated |
hsa-miR-628-3p *,** | Up-regulated | Up-regulated |
hsa-miR-873-5p * | Up-regulated | Down-regulated |
hsa-miR-877-5p * | Down-regulated | Down-regulated |
KEGG Pathways | p-Value | # Genes | # miRNAs | miRNAs |
---|---|---|---|---|
1. Hippo signaling pathway | 6.14 × 10−5 | 32 | 4 | miR-1305, miR-628-3p, miR-1185-5p, miR-877-5p |
2. Thyroid hormone signaling pathway | 0.001291 | 32 | 5 | miR-1305, miR-2116-5p, miR-1185-5p, miR-628-3p, miR-877-5p |
3. Mucin type O-Glycan biosynthesis | 0.001804 | 7 | 1 | miR-1305 |
4. TGF-beta signaling pathway | 0.002344 | 19 | 2 | miR-1305, miR-2116-5p |
5. Signaling pathways regulating pluripotency of stem cells | 0.002344 | 35 | 4 | miR-1305, miR-877-5p, miR-628-3p, miR-2116-5p |
6. FoxO signaling pathway | 0.002454 | 35 | 4 | miR-628-3p, miR-1185-5p, miR-1305, miR-2116-5p |
7. Gap junction | 0.009118 | 21 | 4 | miR-1305, miR-2116-5p, miR-628-3p, miR-877-5p |
8. Long-term potentiation | 0.014921 | 20 | 5 | miR-1305, miR-1185-5p, miR-628-3p, miR-877-5p, miR-2116-5p |
9. RNA transport | 0.01845 | 37 | 5 | miR-1305, miR-1185-5p, miR-628-3p, miR-877-5p, miR-2116-5p |
10. Dopaminergic synapse | 0.036055 | 30 | 4 | miR-1185-5p, miR-1305, miR-2116-5p, miR-628-5p |
AA | EA | p-Value | |
---|---|---|---|
Age (yrs) | 49.814 ± 11.120 | 52.523 ± 13.741 | p = 0.1326 |
(n = 74) | (n = 48) | ||
Tumor size (cm) | 3.380 ± 2.910 | 3.023 ± 6.516 | p = 0.3583 |
(n = 73) | (n = 44) | ||
Tumor grade | |||
1 + 2 | 11 | 5 | p ≥ 0.05 |
3 | 63 | 40 | |
(n = 74) | (n = 45) | ||
Ki67 | |||
≤14 (low) | 4 | 2 | p ≥ 0.05 |
>14 (high) | 41 | 21 | |
(n = 45) | (n = 23) | ||
Vital status | |||
Alive | 40 | 31 | p ≥ 0.05 |
Deceased | 37 | 21 | |
(n = 77) | (n = 52) |
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Bhattarai, S.; Sugita, B.M.; Nunes-Souza, E.; Fonseca, A.S.; Chandrashekar, D.S.; Bhargava, M.; Cavalli, L.R.; Aneja, R. Dysregulated miRNA Expression and Androgen Receptor Loss in Racially Distinct Triple-Negative Breast Cancer. Int. J. Mol. Sci. 2024, 25, 13679. https://doi.org/10.3390/ijms252413679
Bhattarai S, Sugita BM, Nunes-Souza E, Fonseca AS, Chandrashekar DS, Bhargava M, Cavalli LR, Aneja R. Dysregulated miRNA Expression and Androgen Receptor Loss in Racially Distinct Triple-Negative Breast Cancer. International Journal of Molecular Sciences. 2024; 25(24):13679. https://doi.org/10.3390/ijms252413679
Chicago/Turabian StyleBhattarai, Shristi, Bruna M. Sugita, Emanuelle Nunes-Souza, Aline S. Fonseca, Darshan Shimoga Chandrashekar, Mahak Bhargava, Luciane R. Cavalli, and Ritu Aneja. 2024. "Dysregulated miRNA Expression and Androgen Receptor Loss in Racially Distinct Triple-Negative Breast Cancer" International Journal of Molecular Sciences 25, no. 24: 13679. https://doi.org/10.3390/ijms252413679
APA StyleBhattarai, S., Sugita, B. M., Nunes-Souza, E., Fonseca, A. S., Chandrashekar, D. S., Bhargava, M., Cavalli, L. R., & Aneja, R. (2024). Dysregulated miRNA Expression and Androgen Receptor Loss in Racially Distinct Triple-Negative Breast Cancer. International Journal of Molecular Sciences, 25(24), 13679. https://doi.org/10.3390/ijms252413679