Search

Neurological and neuropsychiatric disorders pose substantial challenges to public health, necessitating a comprehensive understanding of the molecular mechanisms underlying their pathogenesis. In recent years, the focus has shifted toward the intricate world of non-coding RNAs (ncRNAs), a class of RNA molecules that do not encode proteins but play pivotal roles in gene regulation and cellular processes. This review explores the emerging significance of ncRNAs in the context of neurological and neuropsychiatric disorders, shedding light on their diverse functions and regulatory mechanisms. The dysregulation of various ncRNAs, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), has been implicated in the pathophysiology of conditions such as Alzheimer's disease, Parkinson's disease, schizophrenia, and mood disorders. This review delves into the specific roles these ncRNAs play in modulating key cellular processes, including synaptic plasticity, neuroinflammation, and apoptosis, providing a nuanced understanding of their impact on disease progression. Furthermore, it discusses the potential diagnostic and therapeutic implications of targeting ncRNAs in neurological and neuropsychiatric disorders. The identification of specific ncRNA signatures holds promise for the development of novel biomarkers for early disease detection, while the manipulation of ncRNA expression offers innovative therapeutic avenues. Challenges and future directions in the field are also considered, highlighting the need for continued research to unravel the complexities of ncRNA-mediated regulatory networks in the context of neurological and neuropsychiatric disorders. This review aims to provide a comprehensive overview of the current state of knowledge and stimulate further exploration into the fascinating realm of ncRNAs in the brain's intricate landscape. [ABSTRACT FROM AUTHOR]

The NLRP3 inflammasome plays a pivotal role in regulating inflammation and immune responses. Its activation can lead to an inflammatory response and pyroptotic cell death. This is beneficial in the case of infections, but excessive activation can lead to chronic inflammation and tissue damage. Moreover, while most of the mammalian genome is transcribed as RNAs, only a small fraction codes for proteins. Among non-protein-coding RNAs, long non-coding RNAs (lncRNAs) have been shown to play key roles in regulating gene expression and cellular processes. They interact with DNA, RNAs, and proteins, and their dysregulation can provide insights into disease mechanisms, including NLRP3 inflammasome activation. Here, we systematically analyzed previously published RNA sequencing (RNA-seq) data of NLRP3 inflammasome activation in monocytes/macrophages to uncover inflammasome-regulated lncRNA genes. To uncover the functional importance of inflammasome-regulated lncRNA genes, one inflammasome-regulated lncRNA, ENSG00000273124, was knocked down in an in vitro model of macrophage polarization. The results indicate that silencing of ENSG00000273124 resulted in the up-regulation tumor necrosis factor (TNF), suggesting that this lncRNA might be involved in pro-inflammatory response in macrophages. To make our analyzed data more accessible, we developed the web database InflammasomeDB. [ABSTRACT FROM AUTHOR]

Cancer and cardiovascular disease are the leading causes of death worldwide. Recent evidence suggests that these two life-threatening diseases share several features in disease progression, such as angiogenesis, fibrosis, and immune responses. This has led to the emergence of a new field called cardio-oncology. Doxorubicin is a chemotherapy drug widely used to treat cancer, such as bladder and breast cancer. However, this drug causes serious side effects, including acute ventricular dysfunction, cardiomyopathy, and heart failure. Based on this evidence, we hypothesize that comparing the expression profiles of cells and tissues treated with doxorubicin may yield new insights into the adverse effects of the drug on cellular activities. To test this hypothesis, we analyzed published RNA sequencing (RNA-seq) data from doxorubicin-treated cells to identify commonly differentially expressed genes, including long non-coding RNAs (lncRNAs) as they are known to be dysregulated in diseased tissues and cells. From our systematic analysis, we identified several doxorubicin-induced genes. To confirm these findings, we treated human cardiac fibroblasts with doxorubicin to record expression changes in the selected doxorubicin-induced genes and performed a loss-of-function experiment of the lncRNA MAP3K4-AS1. To further disseminate the analyzed data, we built the web database DoxoDB. [ABSTRACT FROM AUTHOR]

Type II diabetes (T2D) is a growing health problem worldwide due to increased levels of obesity and can lead to other life-threatening diseases, such as cardiovascular and kidney diseases. As the number of individuals diagnosed with T2D rises, there is an urgent need to understand the pathogenesis of the disease in order to prevent further harm to the body caused by elevated blood glucose levels. Recent advances in long non-coding RNA (lncRNA) research may provide insights into the pathogenesis of T2D. Although lncRNAs can be readily detected in RNA sequencing (RNA-seq) data, most published datasets of T2D patients compared to healthy donors focus only on protein-coding genes, leaving lncRNAs to be undiscovered and understudied. To address this knowledge gap, we performed a secondary analysis of published RNA-seq data of T2D patients and of patients with related health complications to systematically analyze the expression changes of lncRNA genes in relation to the protein-coding genes. Since immune cells play important roles in T2D, we conducted loss-of-function experiments to provide functional data on the T2D-related lncRNA USP30-AS1, using an in vitro model of pro-inflammatory macrophage activation. To facilitate lncRNA research in T2D, we developed a web application, T2DB, to provide a one-stop-shop for expression profiling of protein-coding and lncRNA genes in T2D patients compared to healthy donors or subjects without T2D. [ABSTRACT FROM AUTHOR]

Crohn disease (CD) is a type of inflammatory bowel disease that causes inflammation in the digestive tract. Cases of CD are increasing worldwide, calling for more research to elucidate the pathogenesis of CD. For this purpose, the usage of the RNA-sequencing (RNA-seq) technique is increasingly appreciated, as it captures RNA expression patterns at a particular time point in a high-throughput manner. Although many RNA-seq datasets are generated from CD patients and compared to those of healthy donors, most of these datasets are analyzed only for protein-coding genes, leaving non-coding RNAs (ncRNAs) undiscovered. Long non-coding RNAs (lncRNAs) are any ncRNAs that are longer than 200 nucleotides. Interest in studying lncRNAs is increasing rapidly, as lncRNAs bind other macromolecules (DNA, RNA, and/or proteins) to finetune signaling pathways. To fill the gap in knowledge about lncRNAs in CD, we performed secondary analysis of published RNA-seq data of CD patients compared to healthy donors to identify lncRNA genes and their expression changes. To further facilitate lncRNA research in CD, we built a web database, CrohnDB, to provide a one-stop-shop for expression profiling of protein-coding and lncRNA genes in CD patients compared to healthy donors. [ABSTRACT FROM AUTHOR]

Characterized by cardiovascular disease and diabetes, cardiometabolic diseases are a major cause of mortality around the world. As such, there is an urgent need to understand the pathogenesis of cardiometabolic diseases. Increasing evidence suggests that most of the mammalian genome are transcribed as RNA, but only a few percent of them encode for proteins. All of the RNAs that do not encode for proteins are collectively called non-protein-coding RNAs (ncRNAs). Among these ncRNAs, long ncRNAs (lncRNAs) are considered as missing keys to understand the pathogeneses of various diseases, including cardiometabolic diseases. Given the increased interest in lncRNAs, in this study, we will summarize the latest trend in the lncRNA research from the perspective of cardiometabolism and disease by focusing on the major risk factors of cardiometabolic diseases: obesity, cholesterol, diabetes, and hypertension. Because genetic inheritance is unavoidable in cardiometabolic diseases, we paid special attention to the genetic factors of lncRNAs that may influence cardiometabolic diseases. [ABSTRACT FROM AUTHOR]

Although cardiac tumor formation is rare, accumulating evidence suggests that the two leading causes of deaths, cancers, and cardiovascular diseases are similar in terms of pathogenesis, including angiogenesis, immune responses, and fibrosis. These similarities have led to the creation of new exciting field of study called cardio-oncology. Here, we review the similarities between cancer and cardiovascular disease from the perspective of microRNAs (miRNAs). As miRNAs are well-known regulators of translation by binding to the 3′-untranslated regions (UTRs) of messenger RNAs (mRNAs), we carefully dissect how a specific set of miRNAs are both oncomiRs (miRNAs in cancer) and myomiRs (muscle-related miRNAs). Furthermore, from the standpoint of similar pathogenesis, miRNAs categories related to the similar pathogenesis are discussed; namely, angiomiRs, Immune-miRs, and fibromiRs. [ABSTRACT FROM AUTHOR]

The largest solid organ in humans, the liver, performs a variety of functions to sustain life. When damaged, cells in the liver can regenerate themselves to maintain normal liver physiology. However, some damage is beyond repair, which necessitates liver transplantation. Increasing rates of obesity, Western diets (i.e., rich in processed carbohydrates and saturated fats), and cardiometabolic diseases are interlinked to liver diseases, including non-alcoholic fatty liver disease (NAFLD), which is a collective term to describe the excess accumulation of fat in the liver of people who drink little to no alcohol. Alarmingly, the prevalence of NAFLD extends to 25% of the world population, which calls for the urgent need to understand the disease mechanism of NAFLD. Here, we performed secondary analyses of published RNA sequencing (RNA-seq) data of NAFLD patients compared to healthy and obese individuals to identify long non-coding RNAs (lncRNAs) that may underly the disease mechanism of NAFLD. Similar to protein-coding genes, many lncRNAs are dysregulated in NAFLD patients compared to healthy and obese individuals, suggesting that understanding the functions of dysregulated lncRNAs may shed light on the pathology of NAFLD. To demonstrate the functional importance of lncRNAs in the liver, loss-of-function experiments were performed for one NAFLD-related lncRNA, LINC01639, which showed that it is involved in the regulation of genes related to apoptosis, TNF/TGF, cytokine signaling, and growth factors as well as genes upregulated in NAFLD. Since there is no lncRNA database focused on the liver, especially NAFLD, we built a web database, LiverDB, to further facilitate functional and mechanistic studies of hepatic lncRNAs. [ABSTRACT FROM AUTHOR]

The cardiopulmonary system delivers oxygen throughout the body via blood circulation. It is an essential part of the body to sustain the lives of organisms. The integral parts of the cardiopulmonary system—the heart and lungs—are constantly exposed to damaging agents (e.g., dust, viruses), and can be greatly affected by injuries caused by dysfunction in tissues (e.g., myocardial infarction). When damaged, mesenchymal cells, such as fibroblasts, are activated to become myofibroblasts to initiate fibrosis as part of a regenerative mechanism. In diseased states, the excess accumulation of extracellular matrices secreted by myofibroblasts results in further dysfunction in the damaged organs. These fibrotic tissues cannot easily be removed. Thus, there is a growing interest in understanding the fibrotic process, as well as finding biomolecules that can be targets for slowing down or potentially stopping fibrosis. Among these biomolecules, the interest in studying long non-coding RNAs (lncRNAs; any non-protein-coding RNAs longer than 200 nucleotides) has intensified in recent years. In this commentary, we summarize the current status of lncRNA research in the cardiopulmonary system by focusing on cardiac and pulmonary fibrosis. [ABSTRACT FROM AUTHOR]

Long non-coding RNAs (lncRNAs) belong to a class of non-protein-coding RNAs with their lengths longer than 200 nucleotides. Most of the mammalian genome is transcribed as RNA, yet only a small percent of the transcribed RNA corresponds to exons of protein-coding genes. Thus, the number of lncRNAs is predicted to be several times higher than that of protein-coding genes. Because of sheer number of lncRNAs, it is often difficult to elucidate the functions of all lncRNAs, especially those arising from their relationship to their binding partners, such as DNA, RNA, and proteins. Due to their binding to other macromolecules, it has become evident that the structures of lncRNAs influence their functions. In this regard, the recent development of epitranscriptomics (the field of study to investigate RNA modifications) has become important to further elucidate the structures and functions of lncRNAs. In this review, the current status of lncRNA structures and functions influenced by epitranscriptomic marks is discussed. [ABSTRACT FROM AUTHOR]

Most long non-coding RNAs (lncRNAs) are expressed at lower levels than protein-coding genes and their expression is often restricted to specific cell types, certain time points during development, and various stress and disease conditions, respectively. To revisit this long-held concept, we focused on fibroblasts, a common cell type in various organs and tissues. Using fibroblasts and changes in their expression profiles during fibrosis as a model system, we show that the overall expression level of lncRNA genes is significantly lower than that of protein-coding genes. Furthermore, we identified lncRNA genes whose expression is upregulated during fibrosis. Using dermal fibroblasts as a model, we performed loss-of-function experiments and show that the knockdown of the lncRNAs LINC00622 and LINC01711 result in gene expression changes associated with cellular and inflammatory responses, respectively. Since there are no lncRNA databases focused on fibroblasts and fibrosis, we built a web application, FibroDB, to further promote functional and mechanistic studies of fibrotic lncRNAs. [ABSTRACT FROM AUTHOR]