Modulatory Role of microRNAs in Triple Negative Breast Cancer with Basal-Like Phenotype
Abstract
:Simple Summary
Abstract
1. Introduction
2. Molecular Classifications of TNBC: Clinical Outcome Implications
3. MicroRNA Dysregulation on TNBC with Basal-Like Phenotype: An Overview
3.1. Main miRNAs and Biology of TNBC with Basal-Like Phenotype
3.2. miRNAs and BRCA Mutations
3.3. miRNAs and Metastatic Process in TNBC with Basal-Like Phenotype
3.4. miRNAs and Therapy in TNBC with Basal-Like Phenotype
4. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Function | MiRNAs | Validated Targets | Biological Function and Effect | Reference |
---|---|---|---|---|
Tumor suppressive (inhibition) | miR-34c | CCND1, CDK4, CDK6, CDC23 | Cell proliferation and apoptosis | [135] |
miR-204-5p | Poor clinical outcome; metastasis and anoikis sensitivity | [136] | ||
miR-126-3p | Cell proliferation and invasion; TNBC outcome; overall survival | [18,137,138,139] | ||
miR-128-3p/5p | MET | Cell migration and invasion; relapse-free survival; discrimination among TNBC with basal vs. non-basal subtypes | [107,140] | |
miR-143/miR-145 | MUC1 | Cell proliferation and invasion | [141] | |
miR-29a, miR-29b, miR-29c, miR-26a, miR-26b, miR-148a, miR-148b | DNMT3b, TGIF2, CREB5, AKT3 | DNA methylation; overall survival; cell proliferation and colony formation; modulation of ER/PR/HER2/CK5/6 expression | [72,87,89,90,92,113] | |
miR-149 | RAP1A, RAP1B, VAV2 | Metastasis; higher tumor stage | [142] | |
miR-155, miR-493, miR-30e, miR-27a | Discrimination among TNBC with core-basal or non-core-basal subtypes and among TNBC patients with high- and low-risk prognoses; diagnostic and prognostic indicators; prediction of outcomes of patient treatment with anthracycline or anthracycline plus taxanes | [25] | ||
MiRlet7c, miR-125b, miR-126, miR-127-3p, miR-143, miR-145, miR-199a-3p | Basal cell type-specific miRNAs | [18,139] | ||
miR-200 family (miR-200b, miR-200a, miR-429, miR-200c, miR-141) | ZEB1, ZEB2, SUZ12, SNAI1, SNAI2, CDH11, CFL2, SEC23A, EPHA2, TRKB | Modulation of EMT-transcriptional inducers; modulate luminal cell type-specific miRNAs; enhanced stem cell self-renewal; cell migration and invasion; suppression of anoikis resistance; poor survival | [95,139,143,144] | |
miR-203a | ΔNp63α, SLUG, AXL | Cell growth and motility; discrimination among TNBC with basal vs. non-basal subtypes; cancer stem cell-like property | [145] | |
miR-205–5p (miR-205) | KLF12, ITGA5, E2F1, LAMC1, ZEB1, ZEB2, Jagged1, PTPRM | Cell invasion, migration, and apoptosis; cancer stem cell-like property; cell growth and metastasis; EMT | [104,105,106,107,136,144] | |
miR-30a-3p, miR-30a-5p, miR-199a-5p, miR-30c-5p | CDH1, YAP1, TWIST, β3-INTEGRIN, ZEB1, ZEB2 | Overall survival and relapse-free survival; discrimination among TNBC with basal vs. non-basal subtypes; modulation of the expression pattern of EMT-related genes; cell proliferation, migration, invasion, and apoptosis; sustainment of angiogenesis | [18,107,146,147] | |
miR-206 | ER | Positive correlation with the expression level of ER and PR and negative correlation with HER2; negative correlation with TNM staging | [148] | |
miR-20b | STAT3, HIF1A | Reduction in the expression of the vascular endothelial growth factor (VEGF) | [149] | |
let-7a-b-c-5p | DICER | Cell proliferation and metastasis; modulation of ER/PR/HER2/CK5/6 expression; disease-free survival and overall survival | [18,72,113,146,150] | |
miR-424-5p | DCLK1 | Cell proliferation, migration, and invasion | [151] | |
miR_375 | SHOX2, LDHB, CPNE8, QKI, EIF5A2 | Reverses the resistance to tamoxifen in breast cancer cells; EMT; cell proliferation, migration, and invasion; modulation of ER/PR/HER2/CK5/6 | [107,113,152,153] | |
miR-425 | [72] | |||
mir-149, mir-218, mir-374b | Cell proliferation, invasion, and colonization; discrimination between BRCA1 and sporadic basal cancers; TNBC outcome; modification of the therapeutic effects of 5-fluorouracil and cyclophosphamide treatments | [75,138] | ||
miR-100, miR-99, miR-214, miR-342 | [18] | |||
Oncogenic (promotion) | miR-182 | CFN, PFN, BRCA1 | Cytoskeleton reorganization; cell proliferation and invasion | [154] |
mir-198 | Discriminate between BRCA1 and sporadic basal cancers | [75] | ||
miR-183 | ITGB1, COL12A1, COL21A1, DICER1, AGO1-2 | Metastasis; discrimination of molecular subtypes of breast cancers; overall survival | [111] | |
miR-206 | DICER1 | Cell growth | [111] | |
miR-181 | ITGB1, TGFβR3 | Strong expression in p53 mutant BLBCs; metastasis and reversion of anoikis resistance through their negative regulation in the TGF-beta signaling pathway | [111,136,155] | |
let-7d-3p, miR-324-5p, miR-203b | DNMT3b | Overall survival and relapse-free survival; cell migration and invasion | [87,107] | |
miR-95-3p | SNX1 | Decreased OS and RFS in patients treated with anthracycline-based chemotherapy; cell proliferation, migration, invasion, and apoptosis | [107] | |
miR-21 | TPM1, PDCD4, PTEN, TGFR2 | Negative correlation with the expression levels of ER and PR and positive correlation with HER2; cell growth, invasion, and metastasis; positive correlation with TNM staging; EMT; cancer stem cell-like property; cytoskeleton reorganization | [148,154] | |
miR-130a/b-3p | PTEN, PIEZO2 | Mediate drug resistance; cell proliferation | [146,156] | |
miR-17, miR−18a, miR−19a, miR−20a, miR−19b e miR-92amiR-18b | Luminal specific-gene sets, tumor low-grading gene sets, ER, PI3K, MET, DROSHA, IL1R1, NPP4B, CDKN1A¸ FAM214A, E2F1, PTEN, mTOR, p70S6, CXCL12, HOXA9, AQP5, RUNX3 | Cell proliferation; modulation of ER/PR/HER2/CK5/6 expression; endocytosis; cell migration, adhesion, remodeling; distinguishment between BL1 and BL2 subgroups; increased autophagy involved in PTX-resistance; metastasis; expression in high-grade TNBC | [18,72,75,78,110,111,112,113,114,146,157,158] | |
miR-211-5p | [146] | |||
miR-500a-3p | [146] | |||
miR-505 | Cell proliferation; modulation of ER/PR/HER2/CK5/6 expression | [113] | ||
miR-106a-b, miR-106b-25 cluster (miR-106b, miR-93) | Luminal specific-gene sets, tumor low-grading gene sets, PI3K, MET | Cell proliferation; modulation of ER/PR/HER2/CK5/6; endocytosis; cell migration, adhesion, and remodeling; expression in high-grade TNBC | [18,72,75,110,112,113,158] | |
miR-146a, miR-146b-5p | BRCA1-2, TNF, FADD, TRADD, IRAK1, NFKBIA | Cell proliferation and apoptosis homologous recombination miR-146a strongly expressed in p53 mutant BLBCs; BRCA1-deficiency direct decrease in miR-146, which consequently determines EGFR overexpression | [18,127,139,155,159] | |
miR-27b-3p | cell proliferation and growth; TNBC outcome | [138] | ||
miR-221/mir-222 | TRPS1, ER, p27/Kip1, p57, SOCS1, CDKN1B, DNMT3b, ADIPOR1 | EMT; cell invasion and migration; progression of the more aggressive ER-negative basal phenotype; conference of resistance to tamoxifen; aberrant DNA hypermethylation | [87,120,149,160] | |
miR-34b | Overall survival and relapse-free survival; cell proliferation, differentiation, and aggressiveness | [161] | ||
miR-362-5p | Sema3A | Cell proliferation, migration, and invasion | [162] | |
miR-155 | TSPAN5 | Promotion of stem cell proliferation and cellular proliferation | [18,163] | |
miR-150 | [18] | |||
miR-142-5p miR-142-3p | PTEN | Cell proliferation and apoptosis | [18,75,164,165] | |
miR-135b | Cell proliferation, AR status, and age | [18,74,75,76,139] | ||
miR-421 | PIEZO2, PDCD4 | Cell proliferation | [156] | |
miR-454-3p | PIEZO2, AKT | Cell proliferation, migration, invasion, and apoptosis | [156] | |
miR-301a-3p, | PTEN, ER, PIEZO2 | Metastasis; suppression of estrogen signaling; poor prognosis | [156] | |
miR-196a-5p, | PIEZO2, SPRED1 | Cell growth and metastasis | [156] | |
miR-455-5p | CDKN1B | Expression in exosomes; poor prognosis in the BLBC subtype; cell cycle process; cell proliferation, invasion, and migration | [166] | |
miR-1255a | SMAD4 | Expression in exosomes and original cells samples; poor overall survival | [166] | |
miR-134 | Expression in p53 mutant BLBCs | [155] | ||
miR-934 | ER, FOXA1, GATA3 (genes involved in luminal lineage) | VGLL1 and miR-934 overexpression maintaining the luminal progenitor phenotype, at least in part mediated by their direct modulation of ER | [167] | |
miR-10a-b | RB1CC1, CHN1 | Metastasis; EMT; Contribution to the invasive progression of DCIS-associated myoepithelial cells into IDC via TGF signaling activation. | [111,168,169] | |
miR-939 | VE-CADHERIN | Disease-free survival; disrupting endothelial junctions and impairment of endothelial cell function; exosome-associated miR-939 increase in tumor cell trans-endothelial migration | [170] | |
miR-9 | CHN1, PDGFR | EMT; formation of vascular-like structures; disease-free survival and distant metastasis–free survival | [171,172] |
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Angius, A.; Cossu-Rocca, P.; Arru, C.; Muroni, M.R.; Rallo, V.; Carru, C.; Uva, P.; Pira, G.; Orrù, S.; De Miglio, M.R. Modulatory Role of microRNAs in Triple Negative Breast Cancer with Basal-Like Phenotype. Cancers 2020, 12, 3298. https://doi.org/10.3390/cancers12113298
Angius A, Cossu-Rocca P, Arru C, Muroni MR, Rallo V, Carru C, Uva P, Pira G, Orrù S, De Miglio MR. Modulatory Role of microRNAs in Triple Negative Breast Cancer with Basal-Like Phenotype. Cancers. 2020; 12(11):3298. https://doi.org/10.3390/cancers12113298
Chicago/Turabian StyleAngius, Andrea, Paolo Cossu-Rocca, Caterina Arru, Maria Rosaria Muroni, Vincenzo Rallo, Ciriaco Carru, Paolo Uva, Giovanna Pira, Sandra Orrù, and Maria Rosaria De Miglio. 2020. "Modulatory Role of microRNAs in Triple Negative Breast Cancer with Basal-Like Phenotype" Cancers 12, no. 11: 3298. https://doi.org/10.3390/cancers12113298