Shizuka Uchida

Aalborg University · Center for RNA Medicine

Rationale: Increasing evidence indicates the presence of long noncoding RNAs (lncRNAs) in various cell types. Airn is an imprinting gene transcribed from the paternal chromosome. It is in antisense orientation to the imprinted, but maternally-derived, Igf2r gene, on which Airn exerts its regulation in cis. Although Airn is highly expressed in the h...

Myogenesis is a complex process required for skeletal muscle formation during embryonic development and for regeneration and growth of myofibers in adults. Accumulating evidence suggests that long non-coding RNAs (lncRNAs) play key roles in regulating cell fate decision and function in various tissues. However, the role of lncRNAs in the regulation...

Studies in epitranscriptomics indicate that RNA is modified by a variety of enzymes. Among these RNA modifications, adenosine to inosine (A-to-I) RNA editing occurs frequently in the mammalian transcriptome. These RNA editing sites can be detected directly from RNA sequencing (RNA-seq) data by examining nucleotide changes from adenosine (A) to guan...

The recent emergence of epitranscriptomics, a field of study that examines RNA modifications, provides a potential avenue for identifying interlinked mechanisms of cardiomyocyte survival and death. To date, over 140 RNA modifications have been identified; these modifications appear important because they can affect the fate of RNAs, including their...

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 orga...

Adenosine to inosine (A-to-I) RNA editing is one of the most frequent RNA modifications found in the mammalian transcriptome. Recent studies clearly indicate that RNA editing enzymes, adenosine deaminase acting on RNAs (ADARs), are upregulated in stressed cells and under dis-ease conditions, suggesting that monitoring RNA editing patterns might be...

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...

Rationale Aortic valve stenosis (AVS) is a major contributor to cardiovascular death in the elderly population worldwide. MicroRNAs (miRNAs) are highly dysregulated in patients with AVS undergoing surgical aortic valve replacement (SAVR). However, miRNA-dependent mechanisms regulating inflammation and calcification or miRNA-mediated cell-cell cross...

Circular RNAs (circRNAs) constitute an abundant class of covalently closed noncoding RNA molecules that are formed by backsplicing from eukaryotic protein-coding genes. Recent studies have shown that circRNAs can act as microRNA or protein decoys, as well as transcriptional regulators. However, the functions of most circRNAs are still poorly unders...

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...

An international project on the human genome revealed that various RNAs (e.g., messenger RNAs, microRNAs, and long noncoding RNAs [lncRNAs] and their subclass circular RNA [circRNA)) are involved in the pathogenesis of different human diseases, including cancer. Recent studies have highlighted the critical roles of lncRNAs and circRNA in pancreatic...

Pancreatic ductal adenocarcinoma (PDAC) is caused by genetic mutations in four genes: KRAS proto-oncogene and GTPase (KRAS), tumor protein P53 (TP53), cyclin-dependent kinase inhibitor 2A (CDKN2A), and mothers against decapentaplegic homolog 4 (SMAD4), also called the big 4. The changes in tumors are very complex, making their characterization in t...

Background: The global pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has swept through every part of the world. Because of its impact, international efforts have been underway to identify the variants of SARS-CoV-2 by genome sequencing and to understand the gene expression ch...

During spaceflight, astronauts are exposed to various physiological and psychological stressors, such as microgravity, sleep deprivation, isolation, confinement, and high ionizing radiation have shown adverse health effects. Therefore, there is an unmet need to develop novel diagnostic tools to predict early alterations in astronauts' health. Small...

The reproducibility of experimental data is an essential part of scientific research as it is the absolute requirement that the results presented in a scientific manuscript must be reproduced by other studies. If such validation fails, which happens rather frequently (1–3), the most integral part of science is violated, which results in inconsisten...

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 carbohydra...

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 dysfuncti...

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder characterized by damage to the intestinal mucosa, which is caused by a combination of factors. These include genetic and epigenetic alterations, environmental influence, microorganism interactions, and immune conditions. Some populations with IBD show a cancer-prone phenotype. Rece...

BACKGROUND: Transcatheter aortic valve replacement (TAVR) is a well-established treatment option for high- and intermediate-risk patients with severe symptomatic aortic valve stenosis. A majority of patients exhibit improvements in left ventricular ejection fraction (LVEF) after TAVR in response to TAVR-associated afterload reduction. However, a sp...

Background and Objective: The recent emergence of epitranscriptomics provides an avenue for identifying RNA modifications implicated in the pathophysiology of human disease. To date, over 170 RNA modifications have been identified; these modifications are important because they can affect the fate of RNAs, including their decay, maturation, splicin...

Scientific advancement is predicated upon the ability of a novel discovery to be independently reproduced and substantiated by others. Despite this inherent necessity, the research community is awash in published studies that cannot be replicated resulting in widespread confusion within the field and waning trust from the general public. In many ca...

During spaceflight, astronauts are exposed to various physiological and psychological stressors that have been associated with adverse health effects. Therefore, there is an unmet need to develop novel diagnostic tools to predict early alterations in astronauts’ health. Small nucleolar RNA (snoRNA) is a type of short non-coding RNA (60–300 nucleoti...

The goal of this study was to develop an atlas of the metabolic, transcriptional, and proteomic changes that occur with pregnancy in the maternal heart. Timed pregnancy studies in FVB/NJ mice revealed significant increases in heart size by day 8 of pregnancy (mid-pregnancy; MP), which was sustained throughout the rest of the term compared with non-...

We are delighted to share with you our eleventh Journal Club and highlight some of the most interesting papers published recently. We hope to keep you up-to-date with noncoding RNA research that is outside your study area. The Non-Coding RNA Scientific Board wishes you an exciting and fruitful read.

Fibroblasts play an important role in the pathogenic mechanisms of several socially significant diseases, including pulmonary and cardiovascular fibrosis, liver cirrhosis, systemic sclerosis, progressive kidney disease. The alterations of the epitranscriptome, including more than 170 distinct post-transcriptional RNA modifications or editing events...

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...

The breakthrough technology for reprogramming somatic cells into induced pluripotent stem cells (iPSC) has created a new path for science and medicine. The iPSC technology provides a powerful tool for elucidating the mechanisms of cellular differentiation and cell fate decision as well as to study targets and pathways relevant to pathological proce...

The cardiac extracellular matrix plays essential roles in homeostasis and injury responses. Although the role of fibrillar collagens have been thoroughly documented, the functions of non-fibrillar collagen members remain underexplored. These include a distinct group of non-fibrillar collagens, termed, fibril-associated collagens with interrupted tr...

Benzene is a ubiquitous environmental pollutant abundant in household products, petrochemicals and cigarette smoke. Benzene is a well-known carcinogen in humans and experimental animals; however, little is known about the cardiovascular toxicity of benzene. Recent population-based studies indicate that benzene exposure is associated with an increas...

Benzene is a ubiquitous environmental pollutant. Recent population-based studies suggest that benzene exposure is associated with an increased risk for cardiovascular disease. However, it is unclear whether benzene exposure by itself is sufficient to induce cardiovascular toxicity. We examined the effects of benzene inhalation (50 ppm, 6 h/day, 5 d...

Coenzyme A (CoA) is an essential co-factor required for intermediary metabolism. Perturbations in homeostasis of CoA have been implicated in various pathologies; however, whether CoA homeostasis is changed and the extent to which CoA levels contribute to ventricular function and remodeling during pressure overload has not been explored. In this stu...

Benzene is a ubiquitous environmental pollutant. Recent population-based studies suggest that benzene exposure is associated with an increased risk for cardiovascular disease. However, it is unclear whether benzene exposure is sufficient to induce cardiovascular toxicity. We examined the effects of benzene inhalation (50 ppm, 6 h/day, 5 days/week,...

Benzene is a ubiquitous environmental pollutant abundant in household products, petrochemicals and cigarette smoke. Benzene is a well-known carcinogen in humans and experimental animals; however, little is known about the cardiovascular toxicity of benzene. Recent population-based studies indicate that benzene exposure is associated with an increas...

Circular RNAs (circRNAs) are a new class of covalently circularized noncoding RNAs widely expressed in the human heart. Emerging evidence suggests they have a regulatory role in a variety of cardiovascular diseases (CVDs). This review's current focus includes our understanding of circRNA classification, biogenesis, function, stability, degradation...

Long noncoding RNAs have emerged as biomarkers and regulators of cardiovascular disease. However, the expression pattern of circulating extracellular vesicle (EV)-incorporated lncRNAs in patients with coronary artery disease (CAD) is still poorly investigated. A human lncRNA array revealed that certain EV-lncRNAs are significantly dysregulated in C...

It is now commonly accepted that most of the mammalian genome is transcribed as RNA, yet less than 2% of such RNA encode for proteins. A majority of transcribed RNA exists as non-protein-coding RNAs (ncRNAs) with various functions. Because of the lack of sequence homologies among most ncRNAs species, it is difficult to infer the potential functions...

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative virus for the current global pandemic known as coronavirus disease 2019 (COVID-19). SARS-CoV-2 belongs to the family of single-stranded RNA viruses known as coronaviruses, including the MERS-CoV and SARS-CoV that cause Middle East respiratory syndrome (MERS) and severe ac...

Background and Objective: Cardiovascular disease (CVD) is a leading cause of death in industrialized countries. It consists of different etiologies and has linked to other types of diseases (e.g., diabetes, renal failure). Thus, understanding the disease mechanisms of CVD is of a great interest in the cardiovascular field. Because mammalian cardiom...

Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoid malignancy in adults. Although significant progress has been made in recent years to treat DLBCL patients, 30%–40% of the patients eventually relapse or are refractory to first line treatment, calling for better therapeutic strategies for DLBCL. Long non-coding RNAs (lncRNAs) have em...

Although cardiac mesenchymal cell (CMC) therapy mitigates post-infarct cardiac dysfunction, the underlying mechanisms remain unidentified. It is acknowledged that donor cells are neither appreciably retained nor meaningfully contribute to tissue regeneration-suggesting a paracrine-mediated mechanism of action. As the immune system is inextricably l...

This review aims to highlight the recent findings of long non-coding RNAs (lncRNAs) in liver disease. In particular, we focus on the functions of lncRNAs in hepatocellular carcinoma (HCC) and non-alcoholic steatohepatitis (NASH). We summarize the current research trend in lncRNAs and their potential as biomarkers and therapeutic targets for the tre...

Cardiovascular disease is the leading cause of death in pregnant and postpartum women. During pregnancy, the maternal heart rapidly adapts to the increasing physiological and metabolic demands of the growing fetus. This adaptation often takes the form of a physiological hypertrophy in which the maternal heart grows to increase cardiac output; howev...

Chronic inflammation is inextricably linked to cardiovascular disease (CVD). Macrophages themselves play important roles in atherosclerosis, as well as acute and chronic heart failure. Although the role of macrophages in CVD pathophysiology is well-recognized, little is known regarding the precise mechanisms influencing their function in these cont...

Rationale: Long noncoding RNAs (lncRNAs) are emerging as important regulators of diverse biological functions. Their role in pulmonary arterial hypertension (PAH) remains to be explored. Objectives: To elucidate the role of tyrosine kinase receptor inducing lncRNA (TYKRIL) as a regulator of p53/platelet-derived growth factor receptor β (PDGFRβ)...

Although cell therapy-mediated cardiac repair offers promise for treatment/management of heart failure, lack of fundamental understanding of how cell therapy works limits its translational potential. In particular, whether reparative cells from failing hearts differ from cells derived from non-failing hearts remains unexplored. Here, we assessed di...

Purpose of review: Mounting evidence suggests that long noncoding RNAs (lncRNAs) are essential regulators of gene expression. Although few lncRNAs have been the subject of detailed molecular and functional characterization, it is believed that lncRNAs play an important role in tissue homeostasis and development. In fact, gene expression profiling...

Intrinsic cardiogenic factor expression, a proxy for cardiomyogenic lineage commitment, may be an important determinant of donor cell cardiac reparative capacity in cell therapy applications; however, whether and how this contributes to their salutary effects remain largely ambiguous. Methods: The current study examined the consequences of enhanced...

While a majority of the mammalian genome is transcribed to RNA, mounting evidence indicates that only a minor proportion of these transcriptional products are actually translated into proteins. Since the discovery of the first non-coding RNA (ncRNA) in the 1980s, the field has gone on to recognize ncRNAs as important molecular regulators of RNA act...

Several post-translational modifications figure prominently in ventricular remodeling. The beta-O-linkage of N-acetylglucosamine (O-GlcNAc) to proteins has emerged as an important signal in the cardiovascular system. Although there are limited insights about the regulation of the biosynthetic pathway that gives rise to the O-GlcNAc post-translation...

Background: The majority of the human genome comprises noncoding sequences, which are in part transcribed as long noncoding RNAs (lncRNAs). lncRNAs exhibit multiple functions, including the epigenetic control of gene expression. In this study, the effect of the lncRNA MALAT1 (metastasis-associated lung adenocarcinoma transcript 1) on atheroscleros...

Preclinical investigations support the concept that donor cells more oriented towards a cardiovascular phenotype favor repair. In light of this philosophy, we previously identified HDAC1 as a mediator of cardiac mesenchymal cell (CMC) cardiomyogenic lineage commitment and paracrine signaling potency in vitro—suggesting HDAC1 as a potential therapeu...

Despite advances in bioinformatics, custom scripts remain a source of difficulty, slowing workflow development and hampering reproducibility. Here, we introduce Vectools, a command-line tool-suite to reduce reliance on custom scripts and improve reproducibility by offering a wide range of common easy-to-use functions for table and vector manipulati...

Despite advances in bioinformatics, custom scripts remain a source of difficulty, slowing workflow development and hampering reproducibility. Here, we introduce Vectools, a command-line tool-suite to reduce reliance on custom scripts and improve reproducibility by offering a wide range of common easy-to-use functions for table and vector manipulati...

Recent tools to detect RNA editing have expanded our understanding of epitranscriptomics, linking changes in RNA editing to both disease and normal cellular processes. However, the research community currently lacks tools for determining if change in RNA editing or "differential editing" has occurred. To meet this need, we present DRETools, a comma...

Recent tools to detect RNA editing have expanded our understanding of epitranscriptomics, linking changes in RNA editing to both disease and normal cellular processes. However, the research community currently lacks tools for determining if change in RNA editing or “differential editing” has occurred. To meet this need, we present DRETools, a comma...

Allergic asthma is a chronic inflammatory disease dominated by a CD4 + T helper 2 (Th2) cell signature. The immune response amplifies in self-enforcing loops, promoting Th2-driven cellular immunity and leaving the host unable to terminate inflammation. Posttranscriptional mechanisms, including microRNAs (miRs), are pivotal in maintaining immune hom...

In recent years, the role of RNA has expanded to the extent that protein-coding RNAs are now the minority with a variety of non-coding RNAs (ncRNAs) now comprising the majority of RNAs in higher organisms. A major contributor to this shift in understanding is RNA sequencing (RNA-seq), which allows a largely unconstrained method for monitoring the s...

Skeletal muscle mass is regulated by a complex array of signaling pathways. TGF-β–activated kinase 1 (TAK1) is an important signaling protein, which regulates context-dependent activation of multiple intracellular pathways. However, the role of TAK1 in the regulation of skeletal muscle mass remains unknown. Here, we report that inducible inactivati...

Increasing usage of next-generation sequencing technology will illuminate the extent of RNA modifications, which may affect various pathophysiological conditions. Here, we will highlight one such category of RNA modification called RNA editing, which can be detected from RNA sequencing data by simply modifying the data analysis pipeline using bioin...

Increasing usage of next-generation sequencing technol ogy will illuminate the extent of RNA modifcations,-which may affect various pathophysiological conditions. Here, we will highlight one such category of RNA modifcation called RNA editing, which can be detected from RNA sequencing data by simply modifying the data analysis pipeline using bioinf...

Increasing evidence suggests that the numbers of long non‐coding RNAs (lncRNAs) are more than those of protein‐coding genes in various organisms. Although the detection methods for lncRNAs are being increasingly established, there are advantages and disadvantages that exist for each method. In this opinion article, I highlight the differences betwe...

Background: Exercise promotes metabolic remodeling in the heart, which is associated with physiological cardiac growth; however, it is not known whether or how physical activity-induced changes in cardiac metabolism cause myocardial remodeling. In this study, we tested whether exercise-mediated changes in cardiomyocyte glucose metabolism are impor...

Increasing evidence suggests that the numbers of long non-coding RNAs (lncRNAs) are more than those of protein-coding genes in various organisms. Although the detection methods for lncRNAs are being increasingly established, there are advantages and disadvantages that exist for each method. In this opinion article, I highlight the differences betwe...