MicroRNA-Regulated Signaling Pathways: Potential Biomarkers for Pancreatic Ductal Adenocarcinoma
Abstract
:1. Introduction
2. Signaling Pathways Associated with PDAC
2.1. TGF-β and HGF-MET Signaling Pathways
2.2. JAK–STAT Signaling Pathway
2.3. PI3K–AKT Signaling Pathway
2.4. TP53 Signaling Pathway and Apoptosis
2.5. KRAS Signaling Pathway
2.6. Epidermal Growth Factor Receptor and HER2/neu Signaling Pathways
2.7. Notch and Hedgehog Signaling Pathways
2.8. Wnt/β-Catenin Signaling Pathway
2.9. Cell Cycle Signaling Pathway and p16/CDKN2A Inactivation
2.10. Transcription Factors and DNA Methylation
3. Involvement of Metabolic Stress in PDAC
4. Angiogenesis and miRs in PDAC
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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miRs | Regulation in PDAC | Signaling Pathways Involved | Target Genes | Functional Involvement in PDAC | References |
---|---|---|---|---|---|
let-7 | Down | JAK–STAT K-RAS | STAT3, SOCS3, N-cadherin, ZEB1 | Tumor growth, migration | [53] |
let-7a | Up | NOTCH | JAK, STAT | EMT | [103] |
let-7d | Up | K-RAS | KRAS | Cell proliferation, migration, invasion, apoptosis | [81] |
miR-21 | Up | PI3K–AKT K-RAS EGFR Cell cycle Apoptosis | G12D, p27, p57, FOXO1, Bcl-2, FasL, PI3K, AKT, PTEN, RECK, SPRY2 | Cell cycle arrest, apoptosis, gemcitabine resistance, aggressiveness | [59,82,94] |
miR-23a | Up | Apoptosis | APAF1 | Apoptosis | [76] |
miR-24 | Up | Apoptosis | BIM | Apoptosis, cell cycle | [76] |
miR-26a-5p | Down | HGF–MET | ARMTL2, Cyclin E2, MMP12 | Cell proliferation, migration, survival, EMT | [51] |
miR-27a | Up | K-RAS | Sprouty2 | Cell proliferation, migration, invasion, apoptosis | [85] |
miR-29a | Up | Wnt | MUC1 | Cell proliferation, differentiation, invasion, migration, gemcitabine resistance | [109] |
miR-29c | Down | Wnt | ZD4, FZD5, FRAT2, LRP-6 | Cell proliferation, differentiation, invasion, migration | [108] |
miR-34a | Down | Tp53 NOTCH | NOTCH1/2CDK6, SIRT1 | Cell proliferation, migration, invasion, apoptosis | [71,83] |
miR-96b | Down | K-RAS | KRAS, AKT | Cell proliferation, migration, invasion, apoptosis | [80] |
miR-107 | Up | Cell cycle | Cyclin D1-dependent kinase | Cell proliferation | [114] |
miR-126 | Down | K-RAS | KRAS | Cell proliferation, migration, invasion, apoptosis | [81] |
miR-130b | Down | JAK–STAT | STAT3 | Cell proliferation, invasion | [54,56] |
miR-132 | Up | P16 | Rb1 | G2/M cell cycle arrest, cell proliferation | [129] |
miR-141 | Down | DNA methylation | YAP1, MAP4K4 | Tissue homeostasis, organ size, regeneration | [144] |
miR-143 | Down | K-RAS | KRAS, MMP-2, MMP1 | Tumor growth | [86] |
miR-144 | Down | NOTCH | PRR11 | EMT | [103] |
miR-145 | Down | K-RAS NOTCH | KRAS | Tumor growth, EMT | [86,103] |
miR-146a | Down | EGFR | EGFR, NF-κB, IRAK-1 | Increased tumor growth | [93] |
miR-148a | Down | Cell cycle | CDC25B | Cell proliferation, differentiation, invasion, migration | [121] |
miR-148b | Down | DNA methylation | DNMT1, AMPKa1 | Cell proliferation, differentiation, invasion, migration | [143] |
miR-150 | Up | HER-2/neu | MUC4, IGF-1R | Invasion, migration | [45] |
miR-152 | Down | DNA methylation | DNMT1 | Cell proliferation, differentiation, invasion, migration | [143] |
miR-155 | Up | JAK–STAT Tp53 | SOCS1 TP53-induced nuclear protein 1 gene, FOXO3a, RHOA, SMAD1/5, ZNF652 | Cell invasion, migration, metastasis, generation of reactive oxygen species | [54,57,73] |
miR-181a | Up | PI3K–AKT | PTEN | Migration | [61] |
miR-192 | Up | Cell Cycle | Cyclin D1, cyclin D2, CDK4 | Cell proliferation | [115] |
miR-193b | Down | Cell Cycle | KRAS | G1-phase arrest | [118] |
miR-200 | Up | NOTCH | Jagged1, Maml2,Maml3 | EMT | [102] |
miR-200c | Down | EGFR | MIG6, EP300 | Invasion, migration | [95] |
miR-203 | Up | Tp53 | p53 | Cell proliferation, migration, invasion, apoptosis | [72] |
miR-206 | Down | K-RAS | KRAS, ANXA2 | Decrease in proangiogenic and proinflammatory mediators, tumor growth, progression | [83,84] |
miR-212 | Up | P16 Hedgehog | Rb1 | G2/M cell cycle arrest, cell proliferation | [107,129] |
miR-216a | Down | JAK–STAT | JAK2 | Cell proliferation, invasion | [54,55] |
miR-217 | Down | K-RAS, DNA methylation | KRAS, SIRT1 | Cell proliferation, migration, invasion, apoptosis, metabolism, DNA damage, stress responses, genome stability, cell survival | [79,145] |
miR-220c | Up | PI3K–AKT | MUC4 | EMT | [54] |
miR-221 | Up | PI3K–AKT | Cdk4, p16, E2F, CDKN1B, MMP-2, MMP-9, PUMA, PTEN, MDM2, ICAM-1, P27, BIM, SOD2, STAT5A | Proliferation, migration | [60] |
miR-222 | Up | Tp53 P16 Cell cycle | p53, p27, p57, MMP2, MMP9, PUMA, PTEN, BIM, MMP1, SOD2, STAT5 | Cell proliferation, migration, invasion, apoptosis | [72,120,128] |
miR-223 | Up | Cell Cycle | FBXW7, Cyclin E2 | Cell proliferation, differentiation, invasion, migration | [11,119] |
miR-301a | Up | Cell Cycle | Bim, Bak, Bax, NF-κB | Cell proliferation | [116] |
miR-375 | Down | PI3K–AKT | PDK1 | Cell proliferation, invasion, migration | [54,64] |
miR-421 | Up | TGF-β | SMAD4 | Cell proliferation, migration, invasion | [46] |
miR-424-5p | Up | HGF–MET | SOCS6 | Cell proliferation, migration, survival, EMT | [52] |
miR-483-3p | Up | TGF-β | SMAD4 | Cell proliferation, migration, invasion | [47] |
miR-494 | Down | TGF-β | FOXM1 | Cell proliferation, migration, invasion, increased resistance to gemcitabine | [44] |
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Mortoglou, M.; Wallace, D.; Buha Djordjevic, A.; Djordjevic, V.; Arisan, E.D.; Uysal-Onganer, P. MicroRNA-Regulated Signaling Pathways: Potential Biomarkers for Pancreatic Ductal Adenocarcinoma. Stresses 2021, 1, 30-47. https://doi.org/10.3390/stresses1010004
Mortoglou M, Wallace D, Buha Djordjevic A, Djordjevic V, Arisan ED, Uysal-Onganer P. MicroRNA-Regulated Signaling Pathways: Potential Biomarkers for Pancreatic Ductal Adenocarcinoma. Stresses. 2021; 1(1):30-47. https://doi.org/10.3390/stresses1010004
Chicago/Turabian StyleMortoglou, Maria, David Wallace, Aleksandra Buha Djordjevic, Vladimir Djordjevic, E. Damla Arisan, and Pinar Uysal-Onganer. 2021. "MicroRNA-Regulated Signaling Pathways: Potential Biomarkers for Pancreatic Ductal Adenocarcinoma" Stresses 1, no. 1: 30-47. https://doi.org/10.3390/stresses1010004