miR-125 in Breast Cancer Etiopathogenesis: An Emerging Role as a Biomarker in Differential Diagnosis, Regenerative Medicine, and the Challenges of Personalized Medicine
Abstract
:1. Introduction
2. Clinical Features of BC
2.1. Main Risk Factors of BC
2.2. BC Characterization and Patient Management
3. Epigenetics of BC and the Role of miR-125
3.1. microRNA Nomenclature
3.2. Role of miR in BC
3.3. The miR-125 Family: Molecular Organization and Roles in Human Pathology
3.4. miR-125 and Cancer
3.5. Role of miR-125 in BC
3.6. Further Mining miR-125 Function in BC: Competing Endogenous RNA Networks (ceRNET)
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Gene | Function(s) | Estimated Risk | BC Type | Refs |
---|---|---|---|---|
BRCA1 | DNA repair transcription regulation cell cycle regulation chromatin remodeling | 55–65% by age 70 | TNBC luminal B | [11,25,27,28] |
BRCA2 | DNA repair DNA replication transcription regulation cell cycle regulation mitophagy | ~45% by age 70 | TNBC luminal B | [11,25,28] |
PALB2 | DNA repair | All women: RR 2.3, 95% CI 1.4–3.9 < 50 years: RR 3.0, 95% CI 1.4–5.5 | n/a | [17,25,28] |
PTEN | cell survival cell growth | 85% lifetime | luminal A luminal B | [12,25,26,27,28] |
TP53 | cell cycle regulation | 25% by age 74 | all | [13,25,26,27,28] |
CDH1 | cell adhesion | 39% lifetime | luminal A | [14,25,26,27,28] |
STK11 | cell cycle regulation | 32% by age 60 | n/a | [15,25,28] |
CHEK2 | DNA repair cell cycle regulation apoptosis | Female: RR 1.70, 95% CI 1.3–2.2 Male: RR 10.3, 95% CI 3.5–30.0 | n/a | [16,25,26,27,28] |
BRIP1 | DNA repair | All women: RR 2.0, 95% | n/a | [23,25] |
ATM | DNA repair | RR 2.37, 95% CI 1.5–3.8 | n/a | [18,25,26,27,28] |
Tumor | Node | Metastasis | |||
---|---|---|---|---|---|
Tx | no primary tumor information | Nx | not assessable | Mx | not assessed |
T0 | no primary tumor evidence | N0 | no clinically positive nodes | M0 | no evidence |
TIS | carcinoma in situ (primary sites) | N1 | single, ipsilateral, size < 3 cm | M1 | metastasis present at distance |
T1 | size < 2 cm | N2a | single, ipsilateral, size 3–6 cm | ||
T2 | size 2 to 4 cm | N2b | multiple, ipsilateral, size < 6 cm | ||
T3 | size > 4 cm | N3 | massive/ipsilateral/bilateral/controlateral | ||
T4 | size > 4 cm, pterygoid muscle, base of tongue or skin involved | N3a | ipsilateral node(s), one more than 6 cm | ||
N3b | bilateral | ||||
N4 | controlateral |
miR Name | Target Gene(s) | Affected Cellular Functions | Refs |
---|---|---|---|
miR-21 | PTEN | drug resistance | [65,66] |
miR-21 | LZTFL1 | proliferation and metastasis | [67] |
miR-21 | IGFBP3 TPM1 PCD4 TGF-β1 | proliferation, metastasis, epithelial-to-mesenchymal transition (EMT), apoptosis | [68] |
miR-106a | RAF-1 | invasion and proliferation | [69] |
miR-106a | P53 BAX RUNX3 Bcl-2 ABCG2 | proliferation, colony-forming capacity, migration, invasion, apoptosis, sensitivity to cisplatin | [70,71] |
miR-155 | TRF1 | telomere fragility | [72] |
miR-141 | ANP32E | migration and invasion | [74] |
let-7 | ERCC6 | proliferation, apoptosis | [78] |
miR-335 | ERα IGF1R SP1 ID4 | proliferation, apoptosis | [80] |
miR-335 | c-Met | cell scattering, migration, and invasion | [81] |
miR-126 | VEGFA PIK3R2 | angiogenesis, tumor genesis and growth | [83] |
miR-126 | PIK3R2 | trastuzumab resistance | [84] |
miR-199a/b-3p | PAK4 | migration and invasion | [86] |
miR-199a-3p | mTOR c-Met | cell cycle progression, doxorubicin sensitivity, apoptosis | [87] |
miR-199a-3p | TFAM | resistance to cisplatin | [88] |
miR-199a-3p | TFAM | angiogenesis and metastasis under hypoxia | [89] |
miR-101 | POMP Stmn1 DNMT3A EYA1 VHL SOX2 Jak2 MCL-1 | proliferation, apoptosis, angiogenesis, drug resistance, invasion, metastasis | [91] |
miR-101-3p | COX-2 | migration, metastasis | [92] |
miR-101-3p | EZH2 | migration, invasion, proliferation | [93] |
miR-101-5p | GINS1 | DNA replication | [94] |
miR-9 | FOXO1 | proliferation, migration, invasion | [99] |
miR-9 | STARD13 | EMT, metastasis | [100] |
miR-9 | LIFR | metastasis | [101] |
miR-9 | elf5A2 | resistance to doxorubicin | [102] |
miR-9 | HMGA2 EGR1 IGFBP3 | proliferation, metastasis, EMT, apoptosis | [68] |
miR-9 | PDGFRβ | vasculogenesis | [103] |
miR-200 | PDGFRβ | vasculogenesis | [103] |
let-7a-5p miR-9-5p miR-10b miR-21 miR-22-3p miR-23b-3p miR-25-3p miR-29 miR-34a miR-93-5p miR-99a-5p/-3p miR-100-5p miR-101-3p miR-101-5p miR-126-5p/-3p miR-141-3p miR-143-5p/-3p miR-144-5p/-3p miR-145 miR-155 mir-181b1-5p miR-195-5p miR-199a-5p miR-200a miR-203 miR-203a-3p miR-205 miR-210-3p miR-221/222 miR-373 | n/a | biomarkers | [73,76,87,90,94,95,97,98] |
miR | Organ | Target(s) | Notes | Refs |
---|---|---|---|---|
125 | CNS | n/a | deregulated, pediatric | [130] |
125 | CNS | n/a | deregulated | [131,132] |
125 | CNS | p53, p38MAPK | none | [133] |
125 | CNS | BMF | none | [134] |
125a | ovary | n/a | EMT negative regulator | [144] |
125b | ovary | BCL3 | none | [145] |
125b | ovary | n/a | serum biomarker | [146] |
125b | bladder | E2F3 | none | [147] |
125b | bladder | n/a | urine biomarker | [148] |
125-3p | bladder | n/a | hypoxia regulated | [149] |
125 | bladder | n/a | survival predictor | [150] |
125a | liver | MMP11, VEGF | none | [151] |
125b | liver | Mcl-1, IL6R | none | [152] |
125b | liver | Lin28B2 | none | [153] |
125 | liver | Pokemon | none | [154] |
125 | liver | TRAF6 | none | [155] |
125 | liver | hexokinase II | none | [156] |
125 | liver | FOXM1 | none | [157] |
125 | skin | NCAM | none | [158] |
125 | skin | c-Jun | none | [159] |
125b | skin | MMP13 | none | [160] |
125b | skin | STAT3 | none | [161] |
125 | skin | n/a | deregulated | [162] |
125b | bone | STAT3 | none | [163,164] |
125 | bone | ErbB2 | none | [165] |
125 | bone | BAP1 | none | [166] |
125 | lung | n/a | survival predictor | [167] |
125 | lung | EGFR | none | [168] |
125 | lung | HER2 | trastuzumab resistance | [169] |
125 | lung | MMP13 | none | [170] |
125 | pancreas | n/a | deregulated | [171,172] |
125 | pancreas | NEDD9 | none | [173] |
125 | prostate | n/a | deregulated | [174,175,176] |
125 | prostate | BAK1 | none | [177] |
125 | prostate | p53, PUMA | none | [178] |
125b | thyroid | Foxp3 | cisplatin sensitivity | [179] |
125b | stomach | PPP1CA-Rb | none | [180] |
125a-5p | colon | BCL2, BCL2L12, MCL1 | none | [181] |
125b | kidney | n/a | survival predictor | [182] |
miR | Reg. | Target | Reg. | Cellular Function | Cell Line | Ref. |
---|---|---|---|---|---|---|
miR-125a miR-125b | ↑ ↑ | ERBB2 ERBB3 | ↓ ↓ | migration invasion | SKBR3 | [189] |
miR-125b | ↓ | ETS1 | ↑ | proliferation | BC samples | [190] |
miR-125b | ↓ | MUC1 | ↑ | apoptosis | BT-549 ZR-75-1 | [191] |
miR-125b | ↓ | STARD13 | ↑ | metastasis | MCF-7 MDA-MB-231 | [192] |
miR-125 | ↓ | n/a | n/a | radioresistance | MCF-7 MDA-MB-231 | [193] |
miR-125b | ↑ | n/a | n/a | chemoresistance proliferation apoptosis | blood samples | [194] |
miR-125b | ↑ | BAK1 | ↓ | chemoresistance apoptosis | MDA-435 MDA-436 MDA-231 MCF7 SKBR3 | [195] |
miR-125a-5p miR-125b | ↓ ↓ | n/a | n/a | age-dependent BC formation | BC samples | [196] |
miR-125b | ↓ | MMP11 | ↑ | proliferation migration invasion | T47D SKBR3 | [197] |
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Piergentili, R.; Marinelli, E.; Cucinella, G.; Lopez, A.; Napoletano, G.; Gullo, G.; Zaami, S. miR-125 in Breast Cancer Etiopathogenesis: An Emerging Role as a Biomarker in Differential Diagnosis, Regenerative Medicine, and the Challenges of Personalized Medicine. Non-Coding RNA 2024, 10, 16. https://doi.org/10.3390/ncrna10020016
Piergentili R, Marinelli E, Cucinella G, Lopez A, Napoletano G, Gullo G, Zaami S. miR-125 in Breast Cancer Etiopathogenesis: An Emerging Role as a Biomarker in Differential Diagnosis, Regenerative Medicine, and the Challenges of Personalized Medicine. Non-Coding RNA. 2024; 10(2):16. https://doi.org/10.3390/ncrna10020016
Chicago/Turabian StylePiergentili, Roberto, Enrico Marinelli, Gaspare Cucinella, Alessandra Lopez, Gabriele Napoletano, Giuseppe Gullo, and Simona Zaami. 2024. "miR-125 in Breast Cancer Etiopathogenesis: An Emerging Role as a Biomarker in Differential Diagnosis, Regenerative Medicine, and the Challenges of Personalized Medicine" Non-Coding RNA 10, no. 2: 16. https://doi.org/10.3390/ncrna10020016