Cover -- Title Page -- Copyright -- Contents -- List of Contributors -- Preface -- Acknowledgments -- Part I microRNAs and Toxicology -- Chapter 1 Introduction -- References -- Chapter 2 Environmental Toxicants and Perturbation of miRNA Signaling -- 2.1 Introduction -- 2.2 miRNAs: Description and Biological Significance -- 2.2.1 miRNA Biosynthesis and Processing -- 2.2.2 Interaction of miRNAs with mRNA Targets -- 2.3 Environmental Toxicant-Associated miRNA Perturbations -- 2.3.1 Toxicant Class 1: Carcinogenic Metals (Arsenic and Cadmium) -- 2.3.1.1 Arsenic -- 2.3.1.2 Cadmium -- 2.3.2 Toxicant Class 2: Air Toxicants (Formaldehyde, Diesel Exhaust Particles, Cigarette Smoke) -- 2.3.2.1 Formaldehyde -- 2.3.2.2 Diesel Exhaust Particles (DEPs) -- 2.3.2.3 Cigarette Smoke -- 2.3.3 Toxicant Class 3: Polycyclic Aromatic Hydrocarbon (B(a)P) -- 2.3.4 Toxicant Class 4: Endocrine Disruptors (BPA, DDT, Fludioxonil, Fenhexamid, and Nonylphenol) -- 2.3.4.1 BPA, DDT, Fludioxonil, Fenhexamid -- 2.3.4.2 Nonylphenol (NP) -- 2.4 Conclusions and Future Directions -- Acknowledgments -- References -- Chapter 3 microRNAs in Drug-Induced Liver Toxicity -- 3.1 Introduction -- 3.2 miRNA Tissue Distribution and Abundance -- 3.2.1 miRNA in Solid Tissues -- 3.2.2 microRNA in Body Fluids -- 3.3 miRNA and Drug-Induced Liver Toxicity -- 3.3.1 Acetaminophen -- 3.3.2 Carbon Tetrachloride (CCl_4) -- 3.3.3 2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD) -- 3.3.4 Benzo[a]pyrene -- 3.3.5 Tamoxifen -- 3.3.6 Others -- 3.4 Circulating miRNAs as Potential Biomarkers for Drug-Induced Liver Toxicity -- 3.4.1 Introduction of Circulating miRNAs -- 3.4.1.1 Exosomes -- 3.4.1.2 HDL -- 3.4.1.3 Ago2 -- 3.4.2 Blood miRNAs in Drug-Induced Liver Toxicity -- 3.4.3 Urine miRNAs in Drug-Induced Liver Toxicity -- 3.4.4 Technique Challenges.

3.5 Mechanistic Studies and Perspectives -- Disclaimer -- References -- Chapter 4 Fishing for microRNAs in Toxicology -- 4.1 microRNAs in Toxicology -- 4.2 Fish Models in Toxicology -- 4.2.1 Small Fish Models in Toxicology -- 4.2.2 Large Fish Models in Toxicology -- 4.3 Fish as Models for Studying miRNA Function -- 4.3.1 miRNA Studies in Zebrafish -- 4.3.2 miRNA Studies in Other Fish Models -- 4.4 Application of Fish Models in Toxicity Studies of miRNA Alterations -- 4.4.1 Zebrafish in Toxicity Studies of miRNA Alterations -- 4.4.2 Other Fish Models in Toxicity Studies of miRNA Alterations -- 4.5 Summary -- Acknowledgments -- References -- Part II microRNAs and Disease States -- Chapter 5 microRNAs and Inflammation -- 5.1 Introduction -- 5.2 miRNA Biogenesis and Functions -- 5.3 miRNAs in Hematopoietic Systems -- 5.4 miRNA and Inflammatory Diseases -- 5.5 Regulation of the Immune System -- 5.5.1 Acquired Immunity -- 5.5.2 Innate Immunity -- 5.6 Regulation of miRNA Expression -- 5.6.1 Regulation of miRNA by Cytokines and Bacterial Toxins -- 5.6.2 Regulation of miRNA by Mechanical Stimuli -- 5.7 Select miRNA Regulation of Inflammation -- 5.7.1 miR-146a: Negative Regulator of Immune Response -- 5.7.2 Role of miR-155 in Mediating Inflammatory Responses -- 5.7.3 miR-125a/b -- 5.7.4 miR-181a -- 5.8 Conclusion -- References -- Chapter 6 Regulatory Role of microRNAs in Mutagenesis -- 6.1 Introduction -- 6.2 miRNA Roles in Xenobiotic Metabolism -- 6.3 miRNA Roles in the Cell Cycle -- 6.4 miRNA Roles in DNA Repair -- 6.5 Apoptosis -- 6.6 miRNA Regulation and Mutation Formation -- 6.7 Conclusions -- Disclaimer -- References -- Chapter 7 microRNAs and Cancer -- 7.1 Introduction -- 7.2 miRNAs are Deregulated in Cancer -- 7.3 miRNAs Function as Oncogenes and Tumor Suppressor Genes -- 7.4 miRNAs in Cancer Metastasis.

7.5 miRNAs in Cancer Stem Cells -- 7.6 Mutations in miRNA Loci -- 7.7 Mutations in miRNA Target Genes -- 7.8 Prospective: miRNA as Biomarkers and Therapeutics -- Acknowledgments -- References -- Chapter 8 miRNAs in Cancer Invasion and Metastasis -- 8.1 Introduction -- 8.2 miRNAs and Cancer Invasion and Metastasis -- 8.2.1 miRNAs Involved in Angiogenesis -- 8.2.2 miRNAs Involved in Cancer Cell Detachment, Migration, and Invasion -- 8.2.3 miRNAs Involved in Cancer Cell Intravasation -- 8.2.4 miRNAs Involved in Circulating Cancer Cell Survival -- 8.2.5 miRNAs Involved in Cancer Cell Extravasation -- 8.2.6 miRNAs Involved in Metastatic Colonization -- 8.3 miRNAs as Useful Cancer Prognostic Markers -- 8.4 Future Perspectives -- References -- Chapter 9 The Role of microRNAs in Tumor Progression and Therapy -- 9.1 Introduction -- 9.2 Tumor Progression -- 9.3 Key Signaling Pathways -- 9.3.1 Angiogenesis -- 9.3.2 The Ras Pathway -- 9.3.3 The Epidermal Growth Factor Receptor Pathway -- 9.3.4 The PI3K/Akt Pathway -- 9.4 The miRNAs as Regulators of Tumor Progression -- 9.4.1 Current Therapies to Control Tumor Progression -- 9.4.2 Tumor Promoter miRNAs -- 9.4.2.1 miR-21 -- 9.4.2.2 miR-155 -- 9.4.3 Tumor Suppressor miRNAs -- 9.4.3.1 The miR-200 Family -- 9.4.3.2 miR-146a -- 9.4.3.3 The let-7 Family -- 9.5 Regulation of miRNAs by Novel Anticancer Compounds -- 9.6 Conclusions and Perspectives -- References -- Chapter 10 Current Understanding of microRNAs as Therapeutic Targets in Cancer -- 10.1 Introduction on the Rationale of Using miRNAs as Therapeutics in Cancer -- 10.2 Current Approaches to Target miRNAs -- 10.3 Evidence of Successful miRNA Targeting in Experimental Cancer Models -- 10.4 Open Question: Targeting miRNA Processing in Cancer Cells -- 10.5 Concluding Remarks -- References.

Chapter 11 microRNAs, New Players in Cancer Chemoprevention -- 11.1 Introduction -- 11.2 miRNA and the Natural Products -- 11.2.1 Vitamin A -- 11.2.2 Vitamin B -- 11.2.3 Vitamin D -- 11.2.4 Vitamin E -- 11.2.5 Fatty Acids -- 11.2.6 Curcumin -- 11.2.7 Resveratrol -- 11.2.8 Ellagitannin -- 11.2.9 Genistein -- 11.2.10 Catechins -- 11.2.11 Indoles -- 11.3 miRNA and Pharmaceuticals -- 11.3.1 Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) -- 11.3.2 Estrogen Receptor Antagonist -- 11.4 Perspectives -- Acknowledgments -- References -- Chapter 12 microRNA and Neurodegenerative Diseases -- 12.1 Introduction -- 12.2 miRNAs and Parkinson's Disease -- 12.3 miRNAs and Alzheimer's Disease -- 12.4 miRNAs and Huntington's Disease -- 12.5 Outlook -- Acknowledgments -- References -- Chapter 13 Sleep and microRNAs (miRNAs) in Neurodegenerative Diseases -- 13.1 Sleep and microRNAs (miRNAs) in Neurodegenerative Diseases -- 13.2 miRNAs and Sleep -- 13.3 Aging -- 13.4 Alzheimer's Disease -- 13.5 Parkinson's Disease -- 13.6 Creutzfeldt-Jakob Disease -- 13.7 Huntington's Disease -- 13.8 Multiple Sclerosis -- 13.9 Fronto-Temporal Dementia -- 13.10 Summary -- Acknowledgments -- References -- Chapter 14 Role of microRNAs in Autism Spectrum Disorder -- 14.1 Introduction -- 14.2 Epidemiology of ASD -- 14.3 Etiology of ASD: Genetic Associations -- 14.4 ASD as Multigenic Systemic Disorders -- 14.5 Evidence for Epigenetic Contributions -- 14.6 The Role of microRNAs in Neurodevelopment -- 14.7 microRNAs in Neurodevelopmental and Psychiatric Disorders: An Overview -- 14.8 microRNA Expression Profiles in Autism Spectrum Disorder -- 14.8.1 Evidence for Dysregulated miRNAs in Brain and Blood -- 14.8.2 Identification of Novel Gene Targets of Differentially Expressed miRNAs in ASD.

14.8.3 Brain-Related miRNAs are Differentially Expressed in LCLs from Individuals with ASD -- 14.8.4 Functional Associations of Confirmed Differentially Expressed miRNAs -- 14.9 Conclusions -- Acknowledgments -- References -- Chapter 15 The Emerging Function of Natural Products as Regulators of miRNAs in Human Diseases -- 15.1 Introduction -- 15.2 History of Natural Products as Drugs -- 15.3 Functions of miRNAs in Human Diseases -- 15.4 Regulation of miRNAs using Natural Products -- 15.5 Resveratrol and miRNAs -- 15.6 EGCG and miRNAs -- 15.7 Curcumin and miRNAs -- 15.8 Isoflavone and miRNAs -- 15.9 Metformin miRNA -- 15.10 Traditional Herbs and miRNAs -- 15.11 Polyphenol and miRNAs -- 15.12 Rice and miRNA -- 15.13 Human Breast Milk and miRNAs -- 15.14 Conclusion -- Acknowledgments -- References -- Part III microRNAs and Stem Cells -- Chapter 16 Pluripotency and Early Cell Fate Decisions are Orchestrated by microRNAs -- 16.1 Importance of microRNAs in ES and iPS Cells -- 16.2 Biogenesis and Function of microRNAs -- 16.3 microRNAs Mark ES Cell Identity -- 16.3.1 ES Cell Identity is Characterized by Distinct miRs -- 16.3.2 Mouse ES Cell-Specific miRs -- 16.3.3 Human ES Cell-Specific miRs -- 16.3.4 Self-Renewal of ES Cells is Regulated by Cell Cycle Regulating miRs -- 16.3.5 Differentiation Capacity of ES Cells is Maintained by miRs -- 16.3.6 Isoforms and 3' Variability in ES Cell-Specific miRs -- 16.4 microRNAs Guide Induced Pluripotency -- 16.4.1 Reprogramming Factors Regulate ES Cell-Associated miRs -- 16.4.2 Differentiation of ES and iPS Cells is Prevented by miRs -- 16.4.3 Reprogramming Requires ES Cell-Specific miRs -- 16.5 microRNAs Manipulate Cell Fate Decisions -- 16.5.1 Induction of Early Differentiation is Regulated by miRs.

16.5.2 Major Signaling Pathways in ES Cells Regulated by miRs.