MicroRNAs as Molecular Biomarkers for the Characterization of Basal-like Breast Tumor Subtype
Abstract
:1. Introduction
2. Evolution of the BLBC Classification System
3. Significance of MicroRNAs in Breast Tumor Pathogenesis
3.1. Biogenesis of MicroRNAs
3.2. The Dual Regulatory Roles of MicroRNAs in Cancer
4. MicroRNAs in Basal-like Breast Cancer
4.1. MicroRNAs in the Diagnosis and Substratification of BLBC/TNBC Subtype
4.2. MicroRNAs Identified as OncomiRs or Tumor Suppressors in BLBC/TNBC
4.3. Role of MicroRNAs as Prognostic Indicators in BLBC/TNBC
5. MicroRNAs in Modulation of Drug Resistance in Breast Cancer
6. MicroRNAs as Potential Treatment Options for Breast Cancer
7. Limitations and Challenges of MicroRNA-Based Research
8. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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List of MicroRNA | Functional Role in Breast Cancer | Regulated Expression in Breast Cancer | Target(s) | Reference(s) |
---|---|---|---|---|
miR-10b | OncomiR | Upregulated | HOXD10 | [70,71] |
miR-21 | OncomiR | Upregulated | PDCD4, PTEN | [72] |
miR-155 | OncomiR | Upregulated | SOCS1, TP53INP1, FOXO3, RhoA | [73] |
miR-182-5p | OncomiR | Upregulated | CASP9 | [74] |
miR-191 | OncomiR | Upregulated | DICER1 | [61] |
miR-375 | OncomiR | Upregulated | RASD1 | [75,76] |
miR-425 | OncomiR | Upregulated | DICER1 | [61] |
miR-125 | Tumor suppressor | Downregulated | HuR, HER2, ETS1, Cyclin J, MEGF9 | [73,76,77] |
miR-145 | Tumor suppressor | Downregulated | ARF6, fascin, JAM-A, C-MYC, ROCK1, CCNE2, RTKN, OCT4, MUC1, FSCN1, Rab27a | [78,79] |
miR-200 family | Tumor suppressor | Differential | ZEB1, ZEB2 | [73,76,80,81] |
miR-205 | Tumor suppressor | Downregulated | ZEB1, ZEB2, E2F1, LAMC1, KLF12, NFIB, AMOT, ERp29, HER3, CLCN3, SIP1, Ubc13, HMGB1/3, RunX2, ITGA5, VEGF-A, FGF2 | [73,76,82] |
List of MicroRNA(s) | Sample Subtype | Significance of miRNA Expression | Reference(s) |
---|---|---|---|
miR-21 | BLBC | Increased expression is highly associated with BLBC. | [91] |
miR-101-3p miR-126-3p miR-126-5p miR-144-3p miR-144-5p miR-301a-3p miR-664b-5p | Basal-like TNBC | MiRNA panel differentiated healthy women from patients with basal-like TNBC with a sensitivity and specificity of 84% and 74%, respectively. | [84] |
miR-205-5p miR-224-5p miR-375 | BLBC | BLBC differentiated from non-basal TNBCs. | [92] |
miR-146a miR-26a | TNBC | Significantly upregulated in TNBC relative to non-TNBC. | [93] |
miR-146b miR-148a miR-200a miR-200b | TNBC | Downregulated specifically in TNBC. | [94] |
ER status signature miRNAs: miR-135b miR-190 miR-217 miR-218 miR-299 miR-342 PR status signature miRNAs: miR-377 miR-520f-520c miR-520g miR-527-518a HER2 status signature miRNAs: miR-30e miR-181c miR-302c miR-376b miR-520d | TNBC | The miRNA signatures for ER, PR, and HER2 status were able to predict hormone receptor positivity/negativity with 100% accuracy. Incorporating all three panels together can allow for delineation of TNBC from other subtypes. | [95] |
miR-210-3p miR-105-5p miR-767-5p miR-5683 | TNBC | Upregulated in TNBC. Downregulated in TNBC. | [90] |
MicroRNA | Functional Role in BLBC | BLBC/TNBC | Differential Expression | Validated Target(s) | Reference(s) |
---|---|---|---|---|---|
miR-20a-5p | OncomiR | TNBC | Upregulated | RUNX3 | [97] |
miR-29a | OncomiR | TNBC | Upregulated | SUV420H2 | [47,68] |
miR-29b-3p | OncomiR | TNBC | Upregulated | TRAF3 | [67] |
miR-93 | OncomiR | TNBC | Upregulated | LATS2, JAK1, STAT3, FBXL5, SOX4, EZH1, HMGA2 | [87] |
miR-105-5p | OncomiR | TNBC | Upregulated | AKT1, GRB2 | [90,105] |
miR-135b | OncomiR | BLBC | Upregulated | LATS2 | [98,106] |
miR-136 | Tumor suppressor | TNBC | Downregulated | RASAL2 | [107] |
miR-140 | Tumor suppressor | BLBC | Downregulated | SOX9, ALDH1, TRIM28 | [102,108,109] |
miR-146a | OncomiR | TNBC | Upregulated | BRCA1, NRP2 | [107,110] |
miR-146a-5p | Tumor suppressor | TNBC | Downregulated | SOX5 | [111] |
miR-181a | OncomiR | TNBC | Upregulated | BIM, ATM, BAX | [107] |
miR-181b | OncomiR | TNBC | Upregulated | BIM, ATM | [107] |
miR-182 | OncomiR | TNBC | Upregulated | PFN1, RECK, FOXF2 | [107,112,113] |
miR-182-3p | Tumor suppressor | TNBC | Downregulated | TRF2 | [104] |
miR-200a | Tumor suppressor | BLBC and TNBC | Downregulated | EPHA2, ZEB1, ZEB2 | [94,107] |
miR-200b | Tumor suppressor | BLBC and TNBC | Downregulated | PKCα, ZEB1, ZEB2 | [94,107,114] |
miR-210-3p | OncomiR | TNBC | Upregulated | GPD1L, CYGB | [90,115] |
miR-221 | OncomiR | BLBC and TNBC | Upregulated | ANXA3, PTEN, TRPS1 | [107,116,117,118] |
miR-222 | OncomiR | BLBC | Upregulated | ANXA3, PTEN, TRPS1 | [116,117,118] |
miR-296-5p | Tumor suppressor | BLBC | Downregulated | hTERT | [119] |
miR-342 | OncomiR | BLBC and TNBC | Upregulated | ID4 | [107,120] |
miR-512-5p | Tumor suppressor | BLBC | Downregulated | hTERT | [119] |
miR-767-5p | OncomiR | TNBC | Upregulated | SOCS2 | [90,121] |
miR-3940-3p | OncomiR | TNBC | Upregulated | KLLN | [122] |
MicroRNAs in Panel | BLBC/TNBC | Prognostic Implication | Reference(s) |
---|---|---|---|
miR-155 | TNBC | Significantly associated with overall survival (p < 0.01). | [123,125,126] |
miR-30a-5p miR-30a-3p miR-30c-5p | Basal-like TNBC and TNBC | Dysregulation of miR-30 expression was seen to impede the recurrence free survival. | [92,93,94,95,96,97,98,99,100,101,102,103,104,105,106,107,108,109,110,111,112,113,114,115,116,117,118,119,120,121,122,123] |
miR-30a-3p miR-30a-5p miR-199a-5p miR-203b-5p miR-324-5p let-7d-3p | Basal-like TNBC and TNBC | Panel signatures were significantly associated with decreased overall survival (OS). | [92] |
miR-30a-3p miR-30a-5p miR-30c-5p miR-128-3p let-7d-3p | Basal-like TNBC and TNBC | Panel signatures were significantly associated with decreased relapse-free survival (RFS). | [92] |
miR-95-3p | Basal-like TNBC and TNBC | Elevated expression of miR-95-3p in patients treated with anthracycline chemotherapeutics correlates with a diminished overall survival (p = 0.03) and relapse-free survival (p < 0.01). | [92] |
miR-146a miR-26a miR-10b miR-153 | TNBC | Expression of miR-146a and miR-26a is greater in node-negative TNBC relative to node-positive TNBC (p = 0.04 and 0.01, respectively), whereas miR-10b showed the inverse relationship (p = 0.05). | [93] |
miR-1 | TNBC | MALAT1, a long noncoding RNA upregulated in TNBC, possesses known oncogenic function and has a reciprocal relationship with miR-1 expression. Excessive MALAT1 expression is associated with poor overall survival relative to low. | [127] |
miR-27a miR-30e miR-155 miR-493 | BLBC | Panel signatures were significantly associated with median overall survival (p < 0.01). | [125] |
miR-10b miR-21 miR-31 miR-125b miR-130a-3p miR-155 miR-181a miR-181b miR-451a | TNBC | The listed miRNAs were all found to be dysregulated in TNBC and were found to be associated with pathways of chemotherapy resistance. | [89] |
miR-190a miR-200b-3p miR-512-5p | TNBC | A panel incorporating expression levels of the three listed miRNAs was found to be associated with favorable chemotherapy activity (p = 0.06). | [128] |
miR-125b miR-655 miR-421 miR-16 miR-374a miR-374b miR-497 | TNBC | Panel signatures were significantly associated with median distant disease-free survival (DFS) (p < 0.01). | [126] |
miR-16 miR-155 miR-374a miR-125b | TNBC | Panel signatures were significantly associated with overall survival (p = 0.05). | [126] |
miR-148a miR-200b | TNBC and BLBC | Both miRNAs modulate the E2F pathway, whose function is associated with poor prognosis, and both are significantly under expressed in TNBC. | [94] |
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Tariq, M.; Richard, V.; Kerin, M.J. MicroRNAs as Molecular Biomarkers for the Characterization of Basal-like Breast Tumor Subtype. Biomedicines 2023, 11, 3007. https://doi.org/10.3390/biomedicines11113007
Tariq M, Richard V, Kerin MJ. MicroRNAs as Molecular Biomarkers for the Characterization of Basal-like Breast Tumor Subtype. Biomedicines. 2023; 11(11):3007. https://doi.org/10.3390/biomedicines11113007
Chicago/Turabian StyleTariq, Muhammad, Vinitha Richard, and Michael J. Kerin. 2023. "MicroRNAs as Molecular Biomarkers for the Characterization of Basal-like Breast Tumor Subtype" Biomedicines 11, no. 11: 3007. https://doi.org/10.3390/biomedicines11113007