Preface
Contents
Chapter 1: The Therapeutic Role of MicroRNAs in Human Gliomas
1 Introduction
2 MicroRNAs in Gliomas
3 Oncogenic miRNAs
3.1 miR-21
3.2 miR-182
3.3 miR-10b
3.4 miR-106b
3.5 miR-20a
3.6 miR-183
4 Tumor Suppressor miRNAs
4.1 miR-34a
4.2 miR-25 and miR-32
4.3 miR-107
4.4 miR-124
4.5 miR-218
5 Conclusions
References
Chapter 2: miRNA Expression and Functions in Glioma and Glioma Stem Cells
1 Introduction
1.1 The New Classification of GBM
1.2 The Mesenchymal Transformation of GBM
1.3 The Factors Underlying the Mesenchymal Transformation of GBM
2 Cancer Stem Cells (CSCs)
2.1 General Aspects of Cancer Stem Cells
2.2 Glioma Stem Cells (GSCs)
2.3 miRNAs in Cancer
2.4 miRNAs as Biomarkers in GBM
2.5 miRNA Functions in GBM
2.5.1 Oncogenic miRNAs in GBM
2.5.2 Tumor Suppressor miRNAs in GBM
2.6 miRNAs in Glioma Stem Cells
2.6.1 GSCs Versus NSCs
2.6.2 miRNAs Associated with CD133+ and CD133- Cells
2.6.3 miRNAs Associated with the Differentiation of GSCs
2.7 miRNA Delivery into Brain Tumors
2.8 Vectors for miRNA Delivery
2.9 Exosomes for miRNA Delivery
2.10 Stem Cells for the Delivery of miRNAs
2.11 Pre-clinical Studies in Glioma and GSC-Derived Xenografts
3 Conclusions
References
Chapter 3: The Role of MicroRNA in Lung Cancer Drug Resistance and Targeted Therapy
1 Introduction
2 Drug Resistance in Lung Cancer
2.1 Current Opinion of MDR in Lung Cancer
2.2 Representative Features of MDR
2.3 Molecular Mechanisms of MDR
2.4 miRNA Analysis - A Novel Screening Tool in Lung Cancer Chemotherapy
3 miRNAs in Lung Cancer: Tiny Molecules with Huge Impacts
3.1 miRNAs Altered in Lung Carcinogenesis and Development
3.1.1 miRNAs as Oncogenes-OncomiRs
3.1.2 miRNAs as Tumor Suppressors-Tumor Suppressor miRs
3.2 miRNAs as Biomarkers for Early Diagnosis in Lung Cancer
3.3 miRNAs in Lung Cancer Prognosis
3.4 miRNAs in Lung Cancer Therapy
4 miRNAs in Lung Cancer Drug Resistance
4.1 miR-Polymorphisms and miR-Targeted mRNA Polymorphisms Alter Drug Metabolism
4.2 miRNA Polymorphisms and Drug Resistance
4.3 miRNAs Altered in Drug Resistance
4.3.1 miRNAs Affect Drug Sensitivity to EGFR Mutants
4.3.2 miRNAs Affect TRAIL Resistance
4.3.3 Ectopic Expressions of miRNAs Reverse Therapeutic Effects of Anti-cancer Drugs
5 miRNAs and Lung Cancer Targeted Therapy: Small Molecules with Unlimited Potentials
5.1 miRNAs as New Therapeutic Targets
5.2 miRNA Therapeutics in Lung Cancer
5.3 MiRNA Based-Therapeutic Targets in Invasive and Metastatic Lung Cancer
5.4 Therapeutic Potential of miRNAs in Lung Cancer Chemotherapy
5.5 Therapeutic Potential of miRNAs in Lung Cancer Radiotherapy
6 Conclusion
7 Future Directions
References
Chapter 4: The Potential Role of MicroRNA-Based Therapy for Lung Cancer Stem Cells
1 Introduction
1.1 Lung Cancer and Lung Cancer Stem Cells
1.2 MicroRNA Biogenesis and Function in Lung Cancer
2 MicroRNAs and Their Role in Lung Cancer Stem Cells
2.1 MicroRNA Regulation of Cancer Stem Cells
2.2 MicroRNAs Function in Lung Cancer Stem Cells
3 Therapeutic Potential of Stemness-Related MicroRNAs in Lung Cancer
3.1 MicroRNA Mimic-Based Therapeutics
3.2 MicroRNA Inhibitor-Based Therapeutics
4 Future Perspectives
References
Chapter 5: miRNA Targeted Therapy in Lung Cancer
1 Introduction
2 Resistance to Therapies
2.1 Drug Resistance
2.1.1 Cisplatin
2.1.2 Docetaxel (Taxotere)
2.1.3 EGFR-TKI
2.1.4 Pemetrexed
2.2 Radioresistance
3 miRNA in Diagnosis and Prognosis of Lung Cancer
3.1 miRNAs in Serum/Plasma/Circulation
3.2 miRNAs in Tissue Specimens
3.3 miRNAs in Sputum
4 Targeted Delivery of miRNAs - Challenges and Progress
5 Conclusions
References
Chapter 6: miRNA-Based Ovarian Cancer Diagnosis and Therapy
1 Introduction
2 miRNA Biogenesis and Function
3 miRNAs and Hallmarks of Cancer
4 miRNA Regulation in Cancer
5 miRNA Signature in Cancer
6 Circulating miRNA in Ovarian Cancer
7 miRNAs and Ovarian Cancer Chemoresistance
8 miRNA-Based Therapy
9 Concluding Remarks and Perspectives
References
Chapter 7: Application of MicroRNA in the Treatment and Diagnosis of Cervical Cancer
1 Introduction
2 Mechanism of Action of MicroRNA
3 Relationship Between MicroRNA and Cancer
3.1 Oncogenic MicroRNA
3.2 Tumor Suppressor MicroRNA
4 MicroRNA as a Biomarker
5 MicroRNA as a Therapeutic Target
6 Cervical Cancer and MicroRNA
7 Clinical Application of MicroRNAs in Cervical Cancer
7.1 Diagnosis of Cervical Cancer Based on MicroRNAs
7.2 Treatment of Cervical Cancer Using MicroRNAs
8 Conclusion
References
Chapter 8: Overcoming Drug Resistance in Colorectal Cancer by MicroRNAs
1 Introduction
2 MicroRNAs (miRNAs) Definition and Function
3 Cause of Colorectal Cancer: Multi-genetic Mutations
4 Colon Cancer Stem Cells (CSC): Adult Stem Cells with Accumulated Mutations
5 Cancer Stem Cells (CSCs) and Drug Resistance
6 Micro-RNAs Regulate Cancer Stem Cell Proliferation and Differentiation
6.1 miR-21
6.2 miR-145
7 miRNA and Chemotherapy Resistance in Colorectal Cancer
8 miRNA-Based Therapeutic Strategies
8.1 Blocking Oncogenic miRNAs
8.2 Restoring Expression of Tumour-Suppressor miRNAs in Cancer
9 Conclusion
References
Chapter 9: MicroRNAs as Novel Targets in Liver Cancer: Facing the Clinical Challenge
1 Introduction
2 MicroRNAs in Liver Development, Regeneration and Disease
3 MicroRNAs in Hepatocellular Carcinoma
3.1 MicroRNAs in Hepatocarcinogenesis
3.2 MicroRNAs for Diagnostic and Prognostic Classification
3.3 MicroRNAs as Therapeutic Targets
3.4 Epigenetic Crosstalk in Liver Cancer
3.5 MicroRNAs and Hepatic Cancer Stem Cells
4 Outlook and Conclusions
References
Chapter 10: MicroRNA Based Therapeutic Strategies for Cancer: Emphasis on Advances in Renal Cell Carcinoma
1 Introduction
2 Disruption of miRNAs in Cancer
3 Therapies Targeting miRNAs
3.1 Therapies that Inhibit miRNA Function
3.1.1 Anti-miRNA Oligonucleotides (AMOs)
3.1.2 Antagomirs
3.1.3 Locked Nucleic Acids (LNAs)
3.1.4 Multiple-Target Anti-miRNA Antisense Oligodeoxyribonucleotide (MTg-AMO)
3.1.5 miRNA Sponges
3.1.6 Nanoparticles
3.2 Therapies that Restore miRNA Function
3.2.1 miRNA Mimics
3.2.2 miRNA Genetic Precursors
3.2.3 DNA Demethylating Agents
4 Delivery of Therapeutic MicroRNAs
5 Dose Response and MicroRNA Therapeutics
6 miRNAs in Renal Cancer
7 Closing Remarks and Conclusions
References
Chapter 11: Modulating MicroRNA Expression for the Therapy of Pancreatic Cancer
1 Introduction
2 MicroRNAs as Emerging Therapeutic Targets
3 MicroRNA Targeting in Cancer
3.1 In the Absence of Carriers
3.2 Non Viral Nanovectors
3.3 Viral Vectors
3.4 Route of Administration
4 MicroRNA Targeting in Pancreatic Cancer
5 MicroRNA and Clinical Trials for Cancer
6 Conclusion
References
Chapter 12: MicroRNA Targeted Therapy for Overcoming Drug Resistance, Reversal of EMT and Elimination of Cancer Stem Cells in Prostate and Pancreatic Cancer
1 Introduction
2 The miRNAs in the Regulation of Drug Resistance, EMT and CSCs in Pancreatic Cancer
2.1 miRNA Mediated Regulation of Drug Resistance in Pancreatic Cancer
2.2 miRNA Mediated Regulation of Pancreatic CSCs and EMT in Drug Resistance
3 The miRNAs in the Regulation of Drug Resistance, EMT and CSCs in Prostate Cancer
3.1 miRNA Mediated Regulation of Drug Resistance in Prostate Cancer Cells
3.2 miRNA Mediated Regulation of Prostate CSCs and EMT in Drug Resistance
4 Targeting miRNA for Increasing Drug Sensitivity, Reversing EMT, and Eliminating CSCs in Pancreatic and Prostate Cancers
4.1 Synthetic Small Molecule or Natural Agents for Targeting miRNA
4.2 Oligonucleotide Delivery
5 Conclusions
References
Chapter 13: Modulation of Deregulated MicroRNAs for Target Therapy in Thyroid Cancer
1 Introduction
2 Thyroid Cancer Oncogenes
3 Targeting miRNA in Thyroid Cancer
3.1 MiR-146
3.2 Let-7 Family
3.3 Cluster miR-17-92
3.4 MiR-221 and miR-222
4 Conclusion and Future Perspectives
References
Chapter 14: miRNA-Targeted Therapies in the Most Prevalent Pediatric Solid Tumors
1 Hallmarks of Pediatric Tumors
2 MicroRNAs: A Novel Approach to Treat Pediatric Tumors
2.1 Pediatric Brain Tumors
2.1.1 Medulloblastoma
2.2 Neuroblastoma
2.3 WilmsΒ΄ Tumor
2.4 Rhabdomyosarcoma
2.5 Retinoblastoma
2.6 Osteosarcoma
2.7 EwingΒ΄s Sarcoma
3 Concluding Remarks
References
Chapter 15: Targeting Immune System Through Targeting miRNA for Cancer Therapy
1 Introduction
2 miRNAs and Innate Immunity
2.1 Macrophages
2.2 NK Cells
3 miRNAs and Adaptive Immunity
3.1 B Cells
3.1.1 Related Signalling Pathways in Lymphoma
3.2 T Cells
3.3 Dendritic Cells
4 miRNAs Related to Anti-tumour Immunity
4.1 CNS Involvement
4.2 Cancer in Blood Components
4.3 Gynaecological Cancers
4.4 Cancers of the GI Tract
4.5 Hepatocellular Cancers
4.6 Other Cancers
5 Discussion
6 Current Studies Targeting miRNAs for Therapeutic Purposes
7 Future Challenges and Conclusions
References
Chapter 16: miRNA Regulation of DNA Damage Repair Proteins in Cancer Cells: Interplay of ATM, TRAIL and miRNA
1 Introduction
2 miRNA: Master Regulators of DNA Damage Response
3 ATM Is Involved in Facilitating the Transportation of Pre-miRNA from Nucleus to Cytoplasm
4 MiRNA Regulation by ATM
4.1 ATM Ensures Genomic Stability via HR by Repressing miR-335
4.2 ATM Sufficient Cells Have Over-Expressed Tumor Suppressor miRNA
5 miRNA Subsets Mediated Control of ATM and ATR
5.1 miR-181a/b
5.2 miR-26b and miR-100
5.3 miR-18a and miR-421
5.4 miRNA Mediated Control of Dicer
5.5 ATR Is Regulated by miR-185
6 miRNA Control of BRCA1
7 Wip1 and CDC25 Are Controlled by miR-16
8 miR-34c
9 Genomic Rearrangements Mediated Control of miRNA
10 Diametrically Opposed Role of ATM in Regulation of TRAIL Mediated Apoptosis
Diametrically Opposed Role of ATM in Regulation of TRAIL Mediated Signaling
11 Therapeutic Targets
12 Conclusion
References
Chapter 17: miRNA Regulation of VEGF/VEGFR Signaling
1 Introduction
2 miRNA Biogenesis
3 VEGFR1
3.1 miR-10
3.2 miR-200
4 VEGFR2
4.1 miR-200b and miR-200c
4.2 miR-15
5 VEGFR3
6 VEGF and bFGF Mediated Repression of miRNAs
7 HSPG, NDST-1 and VEGF: Companionship During Signaling
8 DCLK1 Suppresses miRNA Expression
9 miRNAs Enter into HUVECs to Regulate VEGFR
10 Dicer Expression Is Suppressed in Hypoxic HUVECs
11 miRNA Regulation of VEGF-A
11.1 miR-26a
11.2 miR-29a/b
11.3 miR-125a and miR-126
11.4 miR-185
11.5 miR-203 and miR-205
11.6 miR-361-5p and miR-503
11.7 miR-196b
11.8 miR-378
11.9 miR-20b
12 miRNA Regulation of VEGF-C
13 VEGF Regulation
13.1 beta-Catenin
13.2 N-RAS, IRS1 and NF-kappaB1
13.3 Fra-1
13.4 mTOR/p70S6K1
13.5 Specificity Proteins Regulate Expression of VEGF and VEGFR
13.6 HER2 and HER3 Mediated Up-Regulation of VEGF
14 Therapeutic Interventions
14.1 Natural Agents Mediated Inhibition of VEGFR
14.2 Natural Agents Mediated Regulation of miRNA
15 Conclusion
References
Chapter 18: Systems Biology Approaches in the Design of Effective miRNA-Targeted Therapeutics
1 Introduction
2 Systems Analysis to Predict miRNA-mRNA Interactions
3 Identifying Therapy Resistance Sustaining miRNAs Using Systems Approaches
4 Prioritizing miRNAs in Cancer Specimens Using Systems Biology and Pathway Tools
5 Identifying and Targeting Cancer Stem Cell Sustaining miRNAs Using Pathway Analysis Tools
6 Conclusion
References
Index