Extracellular Vesicles as Biomarkers Carriers in Bladder Cancer: Diagnosis, Surveillance, and Treatment
Abstract
:1. Introduction
2. Biology and Function of EVs
3. EVs in Bladder Cancer Pathogenesis
4. EVs as Biomarker Carriers for Bladder Cancer Diagnosis
4.1. Protein Biomarkers
4.2. MicroRNAs and IncRNAs
5. EVs as Biomarkers Carriers for Bladder Cancer Disease Progression and Recurrence
6. EVs as Potential Therapeutic Vectors
7. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
References
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Protein Extracellular Vesicle Biomarkers in Bladder Cancer | |||
---|---|---|---|
Proteins | Effect | Mechanism of Action | Ref. |
Promoters of Oncogenesis | |||
CD36 a | ↑ migration, proliferation and angiogenesis | ↑ Fatty acid uptake | [37] |
5T4 * | ↑ EMT and migration | ↑ CXCL12/CXCR4 chemotaxis ↓ Normal WNT/β-catenin pathway | [37] |
CD44 * | ↑ proliferation, migration and angiogenesis | Adhesion molecule Docking of proteases on cell membrane | [37] |
CD73 (NT5E) a | ↑ angiogenesis, metastases and invasion | Regulates cellular signaling with extracellular matrix components such as fibronectin and laminin | [37] |
CD147 (Basigin) a | ↑ proliferation | Regulates glycolytic metabolic pathways | [37] |
Alpha 1-antitrypsin a,* | ↓ apoptosis | Immunity regulation | [41] |
MAGEB4 a,* | ↑ tumorigenesis and proliferation | ↑ ubiquitination and degradation of various tumor suppressors (p53) | [42] |
NMP-22 | ↑ proliferation | Part of nuclear mitotic apparatus | [42] |
FOLR1 a | ↑ proliferation | ↑ folic uptake in tumor cells ↑ nucleic acid synthesis ↑ STAT3 activation | [60] |
Suppressors of Oncogenesis | |||
TACSTD2 a,** | ↑ apoptosis | Participates in TAp63-dependent apoptosis | [38,39,40] |
H2B1K a,* | ↓ tumorigenesis | Regulates response to DNA damage ↑ Transcriptional expression of tumor suppressor genes | [41] |
TTP1 a | ↑ apoptosis | mitochondrial toxin | [60] |
miRNA Extracellular Vesicle Biomarkers in Bladder Cancer | |||
---|---|---|---|
miRNAs | Effect | Mechanism of Action | Ref. |
Promoters of Oncogenesis | |||
miR-15a-5p a | ↑ proliferation | post transcriptional regulation of MYB oncogene | [45] |
miR-31-5p a | ↑ migration and invasion | MAGI2-AS3/miR-31-5p/TNS1 axis | [45] |
miR-21 a | ↑ invasion | ↓ AKT and MAPK pathways | [45,46] |
miR-155-5p a | ↓ apoptosis | ↓ TP53INP1 expression | [45,56] |
miR-940 a | ↑ proliferation, migration and invasion | ↑ expression of INPP4A, GSK3b, c-MYC, cyclin D, β-catenin ↓ p-27 expression | [46] |
miR-191 a | ↓ apoptosis | ↓ circ-FOXO-3 expression | [46] |
miR-93 a | ↑ drug resistance | ↓ cisplatin-induced apoptosis and regulates LASS2 | [46] |
miR-66-3b b | ↑ proliferation | ↓ TUSC2, p53 and p21 | [47] |
miR-200a-3p a | ↑ invasion | ↑ MMP-2 expression through Dicer/miR-16/JNK2/MMP-2 axis | [46] |
miR-146-5p a | ↑ invasion | ↑ ETS2-Mediated mmp2 mRNA transcription | [56] |
Suppressors of Oncogenesis | |||
miR-205-5p a,* | ↑ apoptosis ↓ EMT and invasion | regulates the expression of the tumor-suppressor protein PTEN targets the transcriptional repressors of E-cadherin, ZEB1 and ZEB2 | [11,46] |
miR-132-3p a | ↑ angiogenesis, migration ↓ invasion and EMT | TGFβ1/Smad2 signaling pathway | [45] |
miR-200c a | ↓ EMT, proliferation and invasion | ↓ ZEB1/2 ↑ E-cadherin ↓ LDHA-induced glycolysis | [46] |
miR-15a a | ↓ proliferation | Targets the oncogene BCL2 | [46] |
miR-30a-3p a | ↓ autophagy ↑ chemosensitivity to cisplatin ↓ invasion | ↓ autophagy-related genes (including ATG5, ATG12, and Beclin-1) ↓ MMP-2 and MMP-9 expression | [46] |
miR-503-5p a | ↓ proliferation | interferes with the Rb/E2F signaling pathway | [46] |
Mirlet7b a,** | ↑ apoptosis ↓ drug resistance | targets MTDH, CALU and MTDH | [46] |
miR-138-5p a | ↑ apoptosis | ↓ Bcl-w and Akt1 protein expression | [56] |
miR-144-5p a | ↓ proliferation | ↓ cell cycle-related genes expression (CCNE1, CCNE2, CDC25A, and PKMYT1) | [56] |
miR-145-5p a | ↓ proliferation and migration | Targets TAGLN2 | [61] |
miR-23b | ↓ EMT induces G0/G1 cell cycle arrest and apoptosis | ↓ expression of Zeb1 | [61] |
miR-133b b | ↑ apoptosis | ↓ Bcl-w and Akt1 protein expression | [69] |
miR-375-3p b | ↓ proliferation and invasion | ↓ expression of FZD8 and therefore blocks the Wnt/β-catenin pathway | [73] |
miR-29c b | ↓ proliferation | suppresses the G1/S cell cycle transition inhibits AKT and GSK-3β phosphorylation | [75] |
RNAs, lncRNAs Extracellular Vesicle Biomarkers in Bladder Cancer | |||
---|---|---|---|
RNAs, lncRNAs | Effect | Mechanism of Action | Ref. |
Promoters of Oncogenesis | |||
GALNT1 a | maintenance of bladder cancer stem cells and bladder tumorigenesis | Mediates O-linked glycosylation of SHH to promote its activation | [44] |
ARHGEF3 a,* | ↑ proliferation and invasion | ↑ expression of Cyclin A2, Cyclin D1, and MMP2 | [44] |
UCA1 a | ↑ proliferation | regulates CREB | [53] |
MALAT1 a | ↓ apoptosis | antagonizes miR-125b | [53,58] |
UCA 201 a | ↑ migration and invasion | ↑ the expression levels of ZEB1 and ZEB2 ↓ expression of hsa-miR-145 and its target gene, the actin-binding protein FSCN1 | [53] |
LINC 0035 a,* | ↑ proliferation, migration and invasion | ↓ miR-466 and LYAR | [53] |
SNHG16 b | ↑ proliferation, migration and invasion | activation of the Wnt/β-catenin pathway↑ expression of STAT3 by ↓ miR-98 expression↓ expression of Bax, cleaved-caspase-3 and cleaved-caspase-9 | [54] |
linc-UBC1 b | ↑ proliferation | binds to PRC2 complex and regulates target gene expression | [54] |
PCAT-1 b,** | ↑ proliferation | ↑ Myc and ↓ BRCA2 | [54,58] |
H19 b | ↑ proliferation, EMT and metastasis | ↓ expression of E-cadherin↑ expression of ID2 | [57] |
Suppressors of Oncogenesis | |||
LASS2 a | ↓ cancer cell invasion and proliferation | ↓ V-ATPase activity, the extracellular hydrogen ion concentration and, in turn, the activation of secreted MMP-2 and MMP-9 | [44] |
FOXO3 a | ↓ proliferation, migration and invasion | ↑ miR-9-5p expression and thus ↓ TGFBR2 expression | [44] |
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Georgantzoglou, N.; Pergaris, A.; Masaoutis, C.; Theocharis, S. Extracellular Vesicles as Biomarkers Carriers in Bladder Cancer: Diagnosis, Surveillance, and Treatment. Int. J. Mol. Sci. 2021, 22, 2744. https://doi.org/10.3390/ijms22052744
Georgantzoglou N, Pergaris A, Masaoutis C, Theocharis S. Extracellular Vesicles as Biomarkers Carriers in Bladder Cancer: Diagnosis, Surveillance, and Treatment. International Journal of Molecular Sciences. 2021; 22(5):2744. https://doi.org/10.3390/ijms22052744
Chicago/Turabian StyleGeorgantzoglou, Natalia, Alexandros Pergaris, Christos Masaoutis, and Stamatios Theocharis. 2021. "Extracellular Vesicles as Biomarkers Carriers in Bladder Cancer: Diagnosis, Surveillance, and Treatment" International Journal of Molecular Sciences 22, no. 5: 2744. https://doi.org/10.3390/ijms22052744