Involvement Of ncRNAs Research Articles

Dynamic non-coding RNA biomarker reveals lung injury and repair induced by polystyrene nanoplastics.

Polystyrene nanoplastics (PS-NPs) are omnipresent in the air and can be inhaled by humans. However, their long-term adverse implications and toxicological mechanisms for human respiratory health are unclear. Therefore, this study aims to provide new insights into the pulmonary toxicity of PS-NPs using mice and organoid models. After subacute and subchronic inhalation of PS-NPs, mice showed pronounced lung injury characterized by respiratory rate changes, altered hematology, and histological evidence of tissue damage and oxidative stress. Similarly, repeated PS-NPs exposure also restricted organoid growth and cause oxidative damage. Notably, through BisqueRNA analysis for a single-cell dataset and canonical markers verification, it was found that PS-NPs induced the emergence and accumulation of transitional cells, suggesting impaired alveolar epithelial repair processes. Sequencing analyses revealed dynamic alterations in non-coding RNA (ncRNA) profiles, including circRNAs and lncRNAs, in response to PS-NPs exposure. Moreover, temporal profiling highlighted distinct sets of ncRNAs as early and progression-associated biomarkers of PS-NP-induced lung injury. These biomarkers correlated with aberrant transitional cells, implicating their roles in disrupted cellular differen tiation and repair mechanisms. Overall, this study observed the multifaceted toxicological responses of PS-NPs to the respiratory system, emphasizing the critical involvement of ncRNAs in mediating PS-NP-induce transitional cells, which was crucial for elucidating the pathophysiology of nanoplastic-induced lung injury and developing targeted therapeutic strategies.

Can stable introns and noncoding RNAs be harnessed to improve health through activation of mitohormesis?

Ever since their introduction a decade ago, stable introns, a type of noncoding (nc)RNAs, are found to be key players in different important cellular processes acting through regulation of gene expression and feedback loops to maintain cellular homeostasis. Despite being commonly regarded as useless byproducts, recent studies in yeast suggested that stable introns are essential for cell survivability under starvation. In Drosophila, we found that a stable intron, sisR-1, has a direct effect in regulating mitochondrial dynamics during short-term fasting and subsequently improved overall oocyte quality. We speculated that the beneficial effects implicated by sisR-1 is through the activation of mitohormesis, an interesting phenomenon in mitochondrial biology. Mitohormesis is suggested to improve health span and lifespan of cells and organisms, but the involvement of ncRNAs is not well-documented. Here, we discuss the potential role of sisR-1 and other ncRNAs in activating mitohormesis and the possible applications in improving cellular and organismal health.

Non-Coding RNAs Extended Omnigenic Module of Cancers.

The emergence of cancers involves numerous coding and non-coding genes. Understanding the contribution of non-coding RNAs (ncRNAs) to the cancer neighborhood is crucial for interpreting the interaction between molecular markers of cancer. However, there is a lack of systematic studies on the involvement of ncRNAs in the cancer neighborhood. In this paper, we construct an interaction network which encompasses multiple genes. We focus on the fundamental topological indicator, namely connectivity, and evaluate its performance when applied to cancer-affected genes using statistical indices. Our findings reveal that ncRNAs significantly enhance the connectivity of affected genes and mediate the inclusion of more genes in the cancer module. To further explore the role of ncRNAs in the network, we propose a connectivity-based method which leverages the bridging function of ncRNAs across cancer-affected genes and reveals the non-coding RNAs extended omnigenic module (NeOModule). Topologically, this module promotes the formation of cancer patterns involving ncRNAs. Biologically, it is enriched with cancer pathways and treatment targets, providing valuable insights into disease relationships.

Non-Coding RNA as Biomarkers and Their Role in the Pathogenesis of Gastric Cancer—A Narrative Review

Non-coding RNAs (ncRNAs) represent a broad family of molecules that regulate gene expression, including microRNAs, long non-coding RNAs and circular RNAs, amongst others. Dysregulated expression of ncRNAs alters gene expression, which is implicated in the pathogenesis of several malignancies and inflammatory diseases. Gastric cancer is the fifth most frequently diagnosed cancer and the fourth most common cause of cancer-related death. Studies have found that altered expression of ncRNAs may contribute to tumourigenesis through regulating proliferation, apoptosis, drug resistance and metastasis. This review describes the potential use of ncRNAs as diagnostic and prognostic biomarkers. Moreover, we discuss the involvement of ncRNAs in the pathogenesis of gastric cancer, including their interactions with the members of major signalling pathways.

The Role of Non-Coding RNAs in Cancer Progression: A Concise Comprehensive Review

Cancer is among one of the most widespread diseases globally and poses a great threat to human wellbeing. Non-coding RNAs (ncRNAs) compose most transcripts but cannot undergo translation. Thus, no proteins are made by them. However, studies have shown that ncRNAs can mimic both oncogenes and tumour suppressor genes involved in cancer. This review discusses recent research on the involvement of ncRNAs in the progression, diagnosis, and treatment of cancer. These ncRNAs consist of microRNAs, long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs). This concise paper aims to inform researchers, clinicians, and scientists in navigating the dynamic field of ncRNAs in cancer with the goal of fostering collaboration to translate discoveries into practical clinical advancements

Extracellular vesicles as carriers for noncoding RNA-based regulation of macrophage/microglia polarization: an emerging candidate regulator for lung and traumatic brain injuries.

Macrophage/microglia function as immune defense and homeostatic cells that originate from bone marrow progenitor cells. Macrophage/microglia activation is historically divided into proinflammatory M1 or anti-inflammatory M2 states based on intracellular dynamics and protein production. The polarization of macrophages/microglia involves a pivotal impact in modulating the development of inflammatory disorders, namely lung and traumatic brain injuries. Recent evidence indicates shared signaling pathways in lung and traumatic brain injuries, regulated through non-coding RNAs (ncRNAs) loaded into extracellular vesicles (EVs). This packaging protects ncRNAs from degradation. These vesicles are subcellular components released through a paracellular mechanism, constituting a group of nanoparticles that involve exosomes, microvesicles, and apoptotic bodies. EVs are characterized by a double-layered membrane and are abound with proteins, nucleic acids, and other bioactive compounds. ncRNAs are RNA molecules with functional roles, despite their absence of coding capacity. They actively participate in the regulation of mRNA expression and function through various mechanisms. Recent studies pointed out that selective packaging of ncRNAs into EVs plays a role in modulating distinct facets of macrophage/microglia polarization, under conditions of lung and traumatic brain injuries. This study will explore the latest findings regarding the role of EVs in the progression of lung and traumatic brain injuries, with a specific focus on the involvement of ncRNAs within these vesicles. The conclusion of this review will emphasize the clinical opportunities presented by EV-ncRNAs, underscoring their potential functions as both biomarkers and targets for therapeutic interventions.

Post-transcriptional regulation of myogenic transcription factors during muscle development and pathogenesis.

The transcriptional regulation of skeletal muscle (SKM) development (myogenesis) has been documented for over 3 decades and served as a paradigm for tissue-specific cell type determination and differentiation. Myogenic stem cells (MuSC) in embryos and adult SKM are regulated by the transcription factors Pax3 and Pax7 for their stem cell characteristics, while their lineage determination and terminal differentiation are both dictated by the myogenic regulatory factors (MRF) that comprise Mrf4, Myf5, Myogenin, and MyoD. The myocyte enhancer factor Mef2c is activated by MRF during terminal differentiation and collaborates with them to promote myoblast fusion and differentiation. Recent studies have found critical regulation of these myogenic transcription factors at mRNA level, including subcellular localization, stability, and translational regulation. Therefore, the regulation of Pax3/7, MRFs and Mef2c mRNAs by RNA-binding factors and non-coding RNAs (ncRNA), including microRNAs and long non-coding RNAs (lncRNA), will be the focus of this review and the impact of this regulation on myogenesis will be further addressed. Interestingly, the stem cell characteristics of MuSC has been found to be critically regulated by ncRNAs, implying the involvement of ncRNAs in SKM homeostasis and regeneration. Current studies have further identified that some ncRNAs are implicated in the etiology of some SKM diseases and can serve as valuable tools/indicators for prediction of prognosis. The roles of ncRNAs in the MuSC biology and SKM disease etiology will also be discussed in this review.

Pulling the trigger: Noncoding RNAs in white adipose tissue browning.

White adipose tissue (WAT) serves as the primary site for energy storage and endocrine regulation in mammals, while brown adipose tissue (BAT) is specialized for thermogenesis and energy expenditure. The conversion of white adipocytes to brown-like fat cells, known as browning, has emerged as a promising therapeutic strategy for reversing obesity and its associated co-morbidities. Noncoding RNAs (ncRNAs) are a class of transcripts that do not encode proteins but exert regulatory functions on gene expression at various levels. Recent studies have shed light on the involvement of ncRNAs in adipose tissue development, differentiation, and function. In this review, we aim to summarize the current understanding of ncRNAs in adipose biology, with a focus on their role and intricate mechanisms in WAT browning. Also, we discuss the potential applications and challenges of ncRNA-based therapies for overweight and its metabolic disorders, so as to combat the obesity epidemic in the future.

Regulation of the Cell Cycle by ncRNAs Affects the Efficiency of CDK4/6 Inhibition.

Cyclin-dependent kinases (CDKs) regulate cell division at multiple levels. Aberrant proliferation induced by abnormal cell cycle is a hallmark of cancer. Over the past few decades, several drugs that inhibit CDK activity have been created to stop the development of cancer cells. The third generation of selective CDK4/6 inhibition has proceeded into clinical trials for a range of cancers and is quickly becoming the backbone of contemporary cancer therapy. Non-coding RNAs, or ncRNAs, do not encode proteins. Many studies have demonstrated the involvement of ncRNAs in the regulation of the cell cycle and their abnormal expression in cancer. By interacting with important cell cycle regulators, preclinical studies have demonstrated that ncRNAs may decrease or increase the treatment outcome of CDK4/6 inhibition. As a result, cell cycle-associated ncRNAs may act as predictors of CDK4/6 inhibition efficacy and perhaps present novel candidates for tumor therapy and diagnosis.

Fine-tuning osteoclastogenesis: An insight into the cellular and molecular regulation of osteoclastogenesis.

Osteoclasts, the bone-resorbing cells, are essential for the bone remodeling process and are involved in the pathophysiology of several bone-related diseases. The extensive corpus of in vitro research and crucial mouse model studies in the 1990s demonstrated the key roles of monocyte/macrophage colony-stimulating factor, receptor activator of nuclear factor kappa B ligand (RANKL) and integrin αvβ3 in osteoclast biology. Our knowledge of the molecular mechanisms by which these variables control osteoclast differentiation and function has significantly advanced in the first decade of this century. Recent developments have revealed a number of novel insights into the fundamental mechanisms governing the differentiation and functional activity of osteoclasts; however, these mechanisms have not yet been adequately documented. Thus, in the present review, we discuss various regulatory factors including local and hormonal factors, innate as well as adaptive immune cells, noncoding RNAs (ncRNAs), etc., in the molecular regulation of the intricate and tightly regulated process of osteoclastogenesis. ncRNAs have a critical role as epigenetic controllers of osteoclast physiologic activities, including differentiation and bone resorption. The primary ncRNAs, which include micro-RNAs, circular RNAs, and long noncoding RNAs, form a complex network that affects gene transcription activities associated with osteoclast biological activity. Greater knowledge of the involvement of ncRNAs in osteoclast biological activities will contribute to the treatment and management of several skeletal diseases such as osteoporosis, osteoarthritis, rheumatoid arthritis, etc. Moreover, we further outline potential therapies targeting these regulatory pathways of osteoclastogenesis in distinct bone pathologies.

Targeting Non-Coding RNAs for the Development of Novel Hepatocellular Carcinoma Therapeutic Approaches.

Hepatocellular carcinoma (HCC) remains a global health challenge, representing the third leading cause of cancer deaths worldwide. Although therapeutic advances have been made in the few last years, the prognosis remains poor. Thus, there is a dire need to develop novel therapeutic strategies. In this regard, two approaches can be considered: (1) the identification of tumor-targeted delivery systems and (2) the targeting of molecule(s) whose aberrant expression is confined to tumor cells. In this work, we focused on the second approach. Among the different kinds of possible target molecules, we discuss the potential therapeutic value of targeting non-coding RNAs (ncRNAs), which include micro interfering RNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs). These molecules represent the most significant RNA transcripts in cells and can regulate many HCC features, including proliferation, apoptosis, invasion and metastasis. In the first part of the review, the main characteristics of HCC and ncRNAs are described. The involvement of ncRNAs in HCC is then presented over five sections: (a) miRNAs, (b) lncRNAs, (c) circRNAs, (d) ncRNAs and drug resistance and (e) ncRNAs and liver fibrosis. Overall, this work provides the reader with the most recent state-of-the-art approaches in this field, highlighting key trends and opportunities for more advanced and efficacious HCC treatments.

Oxidative Stress Modulation by ncRNAs and Their Emerging Role as Therapeutic Targets in Atherosclerosis and Non-Alcoholic Fatty Liver Disease.

Atherosclerosis and non-alcoholic fatty liver disease (NAFLD) are pathologies related to ectopic fat accumulation, both of which are continuously increasing in prevalence. These threats are prompting researchers to develop effective therapies for their clinical management. One of the common pathophysiological alterations that underlies both diseases is oxidative stress (OxS), which appears as a result of lipid deposition in affected tissues. However, the molecular mechanisms that lead to OxS generation are different in each disease. Non-coding RNAs (ncRNAs) are RNA transcripts that do not encode proteins and function by regulating gene expression. In recent years, the involvement of ncRNAs in OxS modulation has become more recognized. This review summarizes the most recent advances regarding ncRNA-mediated regulation of OxS in atherosclerosis and NAFLD. In both diseases, ncRNAs can exert pro-oxidant or antioxidant functions by regulating gene targets and even other ncRNAs, positioning them as potential therapeutic targets. Interestingly, both diseases have common altered ncRNAs, suggesting that the same molecule can be targeted simultaneously when both diseases coexist. Finally, since some ncRNAs have already been used as therapeutic agents, their roles as potential drugs for the clinical management of atherosclerosis and NAFLD are analyzed.

Non-coding RNAs, cancer treatment and cardiotoxicity: A triad of new hope

The global health landscape has experienced a shift towards non-communicable diseases, with cardiovascular diseases and cancer as leading causes of mortality. Although advancements in healthcare have led to an increase in life expectancy, they have concurrently resulted in a greater burden of chronic health conditions. Unintended consequences of anticancer therapies on various tissues, particularly the cardiovascular system, contribute to elevated morbidity and mortality rates that are not directly attributable to cancer. Consequently, the field of cardio-oncology has emerged to address the prevalence of CVD in cancer survivors and the cardiovascular toxicity associated with cancer therapies. Non-coding RNAs (ncRNAs) have been found to play a crucial role in early diagnosis, prognosis, and therapeutics within the realm of cardio-oncology. This comprehensive review evaluates the risk assessment of cancer survivors concerning the acquisition of adverse cardiovascular consequences, investigates the association of ncRNAs with CVD in patients undergoing cancer treatment, and delves into the role of ncRNAs in the diagnosis, treatment, and prevention of CVD in patients with a history of anti-cancer therapy. A thorough understanding of the pathogenesis of cancer therapy-related cardiovascular disease and the involvement of ncRNAs in cardio-oncology will enable healthcare professionals to provide anticancer treatment with minimized cardiovascular side effects, thereby improving patient outcomes. Ultimately, this comprehensive analysis aims to provide valuable insights into the complex interplay between cancer and cardiovascular diseases, facilitating the development of more effective diagnostic, therapeutic, and preventive strategies in the burgeoning field of cardio-oncology.

Metabolic Pathways in Breast Cancer Reprograming: An Insight to Non-Coding RNAs.

Cancer cells reprogram their metabolisms to achieve high energetic requirements and produce precursors that facilitate uncontrolled cell proliferation. Metabolic reprograming involves not only the dysregulation in glucose-metabolizing regulatory enzymes, but also the enzymes engaging in the lipid and amino acid metabolisms. Nevertheless, the underlying regulatory mechanisms of reprograming are not fully understood. Non-coding RNAs (ncRNAs) as functional RNA molecules cannot translate into proteins, but they do play a regulatory role in gene expression. Moreover, ncRNAs have been demonstrated to be implicated in the metabolic modulations in breast cancer (BC) by regulating the metabolic-related enzymes. Here, we will focus on the regulatory involvement of ncRNAs (microRNA, circular RNA and long ncRNA) in BC metabolism, including glucose, lipid and glutamine metabolism. Investigation of this aspect may not only alter the approaches of BC diagnosis and prognosis, but may also open a new avenue in using ncRNA-based therapeutics for BC treatment by targeting different metabolic pathways.

Transcriptome analysis reveals the spinal expression profiles of non-coding RNAs involved in anorectal malformations in rat fetuses

BackgroundDespite improvements in anorectal malformation (ARM) therapy, patients might still experience post-operative problems such as fecal incontinence, constipation, and soiling. In particular, the dysplasia of the lumbosacral spinal cord in ARM patients is a major disorder that affects fecal function post-operation. However, the pathological mechanisms involved are still unclear. MethodsThe non-coding RNAs (ncRNAs) in the lumbosacral spinal cord of fetal rats with ethylenethiourea-induced ARM were identified using RNA sequencing (RNA-seq) and examined to determine their potential function. The lumbosacral spinal cord was isolated on embryonic day 17 for subsequent RNA extraction and RNA-seq. The transcriptome data was analyzed using bioinformatics analysis, followed by validation using quantitative reverse transcription PCR. ResultsCompared to the control group, 26 differentially expressed microRNAs (DEMs; 22 upregulated, 4 downregulated) and 112 differentially expressed long non-coding RNAs (63 upregulated, 49 downregulated) were identified in the ARM group. Several DEMs related to development, namely miR-200a-3p, miR-200b-3p, miR-200c-3p, miR-200a-5p, and miR-429, were selected for further analysis. Notably, compared to the control, the relative expression of miR-200 family members was highly upregulated in ARM fetal rats. Furthermore, GO and KEGG enrichment and miRNA-transcription factor-lncRNA/mRNA network analysis was explored to show molecular mechanism underlying DEMs. ConclusionsOur findings suggest the involvement of ncRNAs, especially the miR-200 family members, in the pathogenesis of lumbosacral spinal cord dysplasia in ARM fetal rats.

Non-Coding RNAs in the Therapeutic Landscape of Pathological Cardiac Hypertrophy.

Cardiovascular diseases are a major health problem, and long-term survival for people diagnosed with heart failure is, still, unrealistic. Pathological cardiac hypertrophy largely contributes to morbidity and mortality, as effective therapeutic approaches are lacking. Non-coding RNAs (ncRNAs) arise as active regulators of the signaling pathways and mechanisms that govern this pathology, and their therapeutic potential has received great attention in the last decades. Preclinical studies in large animal models have been successful in ameliorating cardiac hypertrophy, and an antisense drug for the treatment of heart failure has, already, entered clinical trials. In this review, we provide an overview of the molecular mechanisms underlying cardiac hypertrophy, the involvement of ncRNAs, and the current therapeutic landscape of oligonucleotides targeting these regulators. Strategies to improve the delivery of such therapeutics and overcome the actual challenges are, also, defined and discussed. With the fast advance in the improvement of oligonucleotide drug delivery, the inclusion of ncRNAs-targeting therapies for cardiac hypertrophy seems, increasingly, a closer reality.

Non-coding RNAs associated with autophagy and their regulatory role in cancer therapeutics.

Cancer widely affects the world's health population and ranks second leading cause of death globally. Because of poor prognosis of various types of cancer such as sarcoma, lymphoma, adenomas etc., their high recurrence and metastasis rate and low early diagnosis rate have become concern lately. Role of autophagy in cancer progression is being studied since long. Autophagy is cell's self-degradative mechanism towards stress and has role in degradation of the cytoplasmic macromolecules which has potential to damage other cytosolic molecules. Autophagy can promote as well as inhibit tumorigenesis depending upon the associated protein combinations in cancer cells. Recent studies have shown that non-coding RNAs (ncRNAs) do not code for protein but play essential role in modulation of gene expression. At transcriptional level, different ncRNAs like lncRNAs, miRNAs and circRNAs directly or indirectly affect different stages of autophagy like autophagy-dependent and non-apoptotic cell death in cancer cells. This review focuses on the involvement of ncRNAs in autophagy and the modulation of several cancer signal transduction pathways in cancers such as lung, breast, prostate, pancreatic, thyroid, and kidney cancer.

Advances in the Immune Regulatory Role of Non-Coding RNAs (miRNAs and lncRNAs) in Insect-Pathogen Interactions.

Insects are by far the most abundant and diverse living organisms on earth and are frequently prone to microbial attacks. In other to counteract and overcome microbial invasions, insects have in an evolutionary way conserved and developed immune defense mechanisms such as Toll, immune deficiency (Imd), and JAK/STAT signaling pathways leading to the expression of antimicrobial peptides. These pathways have accessory immune effector mechanisms, such as phagocytosis, encapsulation, melanization, nodulation, RNA interference (RNAi), lysis, autophagy, and apoptosis. However, pathogens evolved strategies that circumvent host immune response following infections, which may have helped insects further sophisticate their immune response mechanisms. The involvement of ncRNAs in insect immunity is undeniable, and several excellent studies or reviews have investigated and described their roles in various insects. However, the functional analyses of ncRNAs in insects upon pathogen attacks are not exhaustive as novel ncRNAs are being increasingly discovered in those organisms. This article gives an overview of the main insect signaling pathways and effector mechanisms activated by pathogen invaders and summarizes the latest findings of the immune modulation role of both insect- and pathogen-encoded ncRNAs, especially miRNAs and lncRNAs during insect–pathogen crosstalk.

Involvement of Non-Coding RNAs in Chemo- and Radioresistance of Nasopharyngeal Carcinoma.

The crucial treatment for nasopharyngeal carcinoma (NPC) is radiation therapy supplemented by chemotherapy. However, long-term radiation therapy can cause some genetic and proteomic changes to produce radiation resistance, leading to tumour recurrence and poor prognosis. Therefore, the search for new markers that can overcome the resistance of tumor cells to drugs and radiotherapy and improve the sensitivity of tumor cells to drugs and radiotherapy is one of the most important goals of pharmacogenomics and cancer research, which is important for predicting treatment response and prognosis. Non-coding RNAs (ncRNAs), such as microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), may play important roles in regulating chemo- and radiation resistance in nasopharyngeal carcinoma by controlling the cell cycle, proliferation, apoptosis, and DNA damage repair, as well as other signalling pathways. Recent research has suggested that selective modulation of ncRNA activity can improve the response to chemotherapy and radiotherapy, providing an innovative antitumour approach based on ncRNA-related gene therapy. Therefore, ncRNAs can serve as biomarkers for tumour prediction and prognosis, play a role in overcoming drug resistance and radiation resistance in NPC, and can also serve as targets for developing new therapeutic strategies. In this review, we discuss the involvement of ncRNAs in chemotherapy and radiation resistance in NPC. The effects of these molecules on predicting therapeutic cancer are highlighted.

The Role of Non-coding RNAs in Alzheimer's Disease: From Regulated Mechanism to Therapeutic Targets and Diagnostic Biomarkers.

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder. AD is characterized by the production and aggregation of beta-amyloid (Aβ) peptides, hyperphosphorylated tau proteins that form neurofibrillary tangles (NFTs), and subsequent neuroinflammation, synaptic dysfunction, autophagy and oxidative stress. Non-coding RNAs (ncRNAs) can be used as potential therapeutic targets and biomarkers due to their vital regulatory roles in multiple biological processes involved in disease development. The involvement of ncRNAs in the pathogenesis of AD has been increasingly recognized. Here, we review the ncRNAs implicated in AD and elaborate on their main regulatory pathways, which might have contributions for discovering novel therapeutic targets and drugs for AD.