Non-coding RNAs at the Cross-Road of Cardiometabolic Diseases and Cancer

This book gives insight into the functional role of non-coding RNAs in central pathways contributing to the development of obesity, type 2 diabetes, non-alcoholic fatty liver disease, atherosclerosis, myocardial infarction, cardiomyopathy, and heart failure. It also sheds light on the relationship of this cluster with cancer. Tumor cells, in contrast to cells in cardiometabolic tissues, can regulate this cluster of non-coding RNAs to escape from oxidative stress and anti-tumor immunity and maintain insulin sensitivity, facilitating cancer progression. The book presents a cluster of non-coding RNAs that may be prospectively analyzed in extensive cohort studies to determine their value in risk-predicting machine learning algorithms. In addition, it emphasizes the role of microvesicles in communication between tumor-adjacent tissue, inflammatory cells, and tumor cells, with a special focus on the role of miR-155. The book intends to promote interdisciplinary research. Due to the comprehensive background information provided in each chapter, it is suitable for researchers in academia and industry and for graduate students in biology, bioengineering, and medicine. Preface 6 Acknowledgments 8 Introduction 9 The Move Towards Cellular Risk Markers 9 Why Non-coding RNA? 9 Objectives 10 Approach 11 Take Home Message 11 References 13 Contents 17 Abbreviations 21 1 Biogenesis and Modes of Action of miRs and Circular and Long Non-coding RNAs 29 1.1 MiRs 29 1.1.1 Biogenesis of miRs 29 1.1.2 MiR Modes of Action 31 1.1.3 Naming of miRs 31 1.1.4 Useful Resources on miRs 32 1.2 Circular RNAs 32 1.2.1 Biogenesis of Circular RNAs 32 1.2.2 Circular RNAs Modes of Action 32 1.2.3 Useful Resources on Circ-RNAs 35 1.3 lncRNAs 35 1.3.1 Biogenesis of lncRNAs 35 1.3.2 Modes of Action of lncRNAs 36 1.4 piRs 39 1.4.1 Biogenesis of piRs 39 1.4.2 Modes of Action of piRs 39 1.4.3 Useful Resources on piRs 41 References 41 2 Non-coding RNAs Related to Obesity 48 2.1 Mechanisms in White Adipogenesis 48 2.1.1 Role of Non-coding RNAs in White Adipogenesis 51 2.2 Inflammation and Insulin Resistance in Obese White Adipose Tissue 52 2.2.1 Role of Non-coding RNAs in Inflammation and Insulin Resistance in Obese White Adipose Tissue 56 2.3 Mechanisms in Brown Adipogenesis and Thermogenesis 57 2.3.1 Role of Non-coding RNAs in Brown Adipogenesis and Thermogenesis 59 2.4 Mechanisms in Browning of White Adipose Tissues 60 2.4.1 Role of Non-coding RNAs in Browning of White Adipose Tissue 61 2.5 Leptin and Insulin in the Hypothalamus 62 2.5.1 Non-coding RNAs Related to Leptin and Insulin in the Hypothalamus 63 References 63 3 Non-coding RNAS Related to Type 2 Diabetes 80 3.1 Mechanisms in β Cell Maturation 80 3.1.1 Non-coding RNAs Related to β Cell Maturation 82 3.2 Mechanisms in Insulin Signaling in the Pancreas 83 3.2.1 Non-coding RNAs in Insulin Signaling in Type 2 Diabetes 86 3.3 Inflammation in the Pancreas, Insulin Resistance, and Type 2 Diabetes 87 3.3.1 Non-coding RNAs Related to Inflammation in the Pancreas, with Insulin Resistance and Type 2 Diabetes 88 References 89 4 Non-coding RNAs Related to Lipid Metabolism and Non-alcoholic Fatty Liver Disease 100 4.1 Cholesterol and Lipids in the Liver 100 4.1.1 Non-coding RNAs and Cholesterol in the Liver 102 4.2 Fatty Acids and Triglycerides 103 4.2.1 Non-coding RNAs and Fatty Acids and Triglycerides 104 4.3 Non-alcoholic Fatty Liver Disease 104 4.3.1 Non-coding RNAs Related to Non-alcoholic Fatty Liver Disease 106 References 108 5 Non-coding RNAs Related to Atherosclerosis 116 5.1 Endothelial Injury, Inflammation, and Apoptosis 116 5.1.1 Non-coding RNAs in Endothelial Injury, Inflammation, and Apoptosis 121 5.2 Fibroproliferative Remodeling and Plaque Destabilization 125 5.2.1 Non-coding RNAs in Fibroproliferative Remodeling and Plaque Destabilization 128 References 129 6 Non-coding RNAs in Cardiomyopathy and Heart Failure 145 6.1 Mechanisms in Cardiomyopathy and Heart Failure 145 6.2 Non-coding RNAs in Cardiomyopathy and Heart Failure 149 6.2.1 Non-coding RNAs in Cardiac Hypertrophy 149 6.2.2 Non-coding RNAs in Cardiac Fibrosis and ECM Deposition 150 6.2.3 Non-coding RNAs in Cardiac Inflammation 152 6.2.4 Non-coding RNAs in Cardiac Angiogenesis 152 6.2.5 Non-coding RNAs in Cardiac Apoptosis 153 6.3 Metabolic Syndrome: The Link Between Metabolic and Cardiovascular Diseases 154 6.3.1 Definition of Metabolic Syndrome 154 6.3.2 Oxidative Stress and Metabolic Syndrome 155 6.3.3 Metabolic Syndrome and Cardiovascular Risk 155 6.3.4 Non-coding RNAs and Metabolic Syndrome Components 156 References 157 7 Non-coding RNAs Related to Cardiometabolic Diseases and Associated to Cancer 174 7.1 Mechanisms of Cancer Progression 174 7.1.1 Induction of Stemness 174 7.1.2 Induction of EMT 178 7.1.3 Induction of Insulin Sensitized State, Cancer Cell Proliferation, and Protection Against Apoptosis 180 7.1.4 Induction of Glycolysis 181 7.1.5 Induction of Angiogenesis 182 7.1.6 Repression of Anti-tumor Immunity and Apoptosis 183 7.1.7 Cancer Cell Proliferation 187 7.1.8 EGFR Signaling and Cancer Progression 189 7.1.9 BMI1 and EZH2 in Cancer Progression 191 7.2 Non-coding RNAs Related to Metabolic and Cardiovascular Diseases Are also Involved in Cancer Progression 192 7.3 Comparison of the Role of Non-coding RNAs in Cardiometabolic Diseases and Cancer 192 References 212 8 Regulation of Non-coding RNAs in Cardiometabolic Tissues and Tumors 237 8.1 Regulation of miRs 237 8.1.1 Hypoxia 239 8.1.2 Glucose 240 8.1.3 Oxidative Stress 243 8.1.4 Inflammation 243 8.1.5 TGF-β 244 8.1.6 MYC 245 8.1.7 Overview 245 8.2 Differences in miR-Profiles in Cardiometabolic Tissues and Tumors May be Due to the Typical Action of lncRNAs and circ-RNAs in Tumors 247 8.3 Action of piRs Particularly in Tumors 248 References 250 9 Communication Between Tumor-Adjacent Tissues and Tumors with Emphasis on Role of Inflammatory Cells 265 9.1 Exchange of miR-Enriched Microvesicles 265 9.2 MiR-155 as a Link Between M1 Macrophage-Mediated Inflammation in Tumor-Adjacent Tissue and Tumor Growth and Metastasis 266 References 268 10 The Impact of Non-coding RNA Networks on Disease Comorbidity: Cardiometabolic Diseases, Inflammatory Diseases, and Cancer 271 10.1 Identification of Non-coding RNAs at Cross-Road of Metabolic and Cardiovascular Diseases 271 10.2 Many Non-coding RNAs at Cross-Road of Metabolic and Cardiovascular Diseases are also Related to Inflammatory Diseases 272 10.3 Differences Between Non-coding RNAs in Cardiometabolic Tissues and Tumors 277 10.4 Expected Technical Developments Underlying the Use of Non-coding RNAs as Biomarkers 278 10.5 The Need for Measuring Fluctuation of Non-coding RNAs 279 References 280