The occurrence of diabetic kidney disease (DKD), a critical microvascular issue in diabetes, is progressively on the rise. In recent years, long noncoding RNAs (lncRNAs) have garnered considerable attention as a novel and critical layer of biological regulation. Our knowledge regarding the roles and underlying mechanisms of lncRNAs in various diseases, including DKD, continues to evolve. Similarly, microRNAs (miRNAs), which are small noncoding RNAs, have been recognized as crucial contributors to cellular processes and disease pathogenesis. Emerging studies have highlighted the complex interactions between lncRNAs and miRNAs, particularly in the context of DKD, underscoring their importance in complex human diseases. Renal intrinsic cell damage is an important cause of inducing DKD. Persistent high glucose stimulation leads to remodeling of renal intrinsic cells and a cascade of pathological changes. This article aims to review recent literature on the lncRNAs-mediated regulation of miRNAs affecting renal intrinsic cells in DKD and to propose novel molecular-level therapeutic strategies for DKD. Through in-depth investigation of this dynamic molecular interaction, we can gain a profound understanding of the potential mechanisms underlying diabetic nephropathy, potentially identifying new targets for therapeutic intervention and paving the way for personalized and effective treatments.

This research investigated how physical activity (PA) might impact the expression of several microRNAs, specifically miR-126, miR-146a, miR-34a, miR-124a, miR-155, and miR-221, in the blood of elderly individuals with type 2 diabetes (T2D). Additionally, the study examined the relationship between these microRNAs and markers of vascular endothelial dysfunction, including vascular endothelial growth factor (VEGF), apolipoprotein A-I (apoA-I), and apolipoprotein B (apoB), to assess their potential in the prevention, early detection, and treatment of diabetes.

This correlational observational study involved 100 male participants, aged between 18 and 65 years, all of whom had been living with type 2 diabetes (T2D) for over six years. The participants were divided into three groups: inactive, moderate, and active, depending on their level of physical activity (PA). Real-time PCR and immunoassays were employed to measure the expression of selected miRNAs, as well as VEGF, apoA-I, apoB, and diabetic management indicators. PA levels were determined using ACTi graph GT1M accelerometer (model WAM 7164; Fort Walton Beach, FL) and energy expenditure was measured in the form of metabolic equivalent (MET) by indirect calorimetry method.

The expression levels of miR-146a, miR-34a, and miR-124a were significantly higher in patients with higher physical activity, while no such increase was observed for the other miRNAs in less active participants. Additionally, PA-active individuals showed a more pronounced decrease in fasting blood sugar (FBS), insulin resistance (IR), fasting insulin (FINS), HOMA-IR, HbA1c (%), and levels of VEGF, apoAI, apoB, and the apoB/apoA-I ratio. The alteration in miRNA expression was positively associated with physical activity, VEGF, apoAI, apoB, the apoB/apoA-I ratio, and diabetes-related metrics, while being inversely related to BMI.

In diabetic patients with higher physical activity levels, circulating miR-146a, miR-34a, and miR-124a showed elevated expression, accompanied by a notable decrease in vascular biomarkers, including apoAI, apoB, and the apoB/apoA-I ratio. The findings revealed a strong correlation between these vascular biomarkers and the physiological responses of miR-146a, miR-34a, and miR-124a, though larger studies are required to validate these results further.

Not applicable.

Lung cancer (LC) is the second most commonly diagnosed cancer among both men and women, and it stands as the leading cause of cancer-related mortality, characterized by high rates of morbidity and mortality. Among its subtypes, non-small cell lung cancer (NSCLC) is the most prevalent and one of the most challenging malignant tumors to treat. To date, various therapeutic approaches, including surgery, radiotherapy, and chemotherapy, have been employed in the management of lung cancer; however, due to its aggressive nature, the survival rates remain low. Consequently, exploring novel treatment strategies is of paramount importance. MicroRNAs (miRNAs), a large family of non-coding RNAs, play crucial roles in regulating several key biological processes, including cell proliferation, differentiation, inflammation, and apoptosis. Among these, microRNA155(miR-155) is one of the most conserved and versatile miRNAs, predominantly overexpressed in various diseases, including malignant tumors. This review elucidates the biological functions and roles of miR-155 in NSCLC and discusses its potential significance as a therapeutic target for future research directions and clinical applications.

Schizophrenia is a complex psychiatric disorder, and genetic and environmental factors have been implicated in its development. Dysregulated glutamatergic and dopaminergic transmission pathways are involved in schizophrenia development. Besides genetic mutations, epigenetic dysregulation has a considerable role in dysregulating molecular pathways involved in schizophrenia. MicroRNAs (miRNAs) are small, non-coding RNAs that target specific mRNAs and inhibit their translation into proteins. As epigenetic factors, miRNAs regulate many genes involved in glutamate and dopamine signaling pathways; thereby, their dysregulation can contribute to the development of schizophrenia. Secretion of specific miRNAs from damaged cells into body fluids can make them one of the ideal non-invasive biomarkers in the early diagnosis of schizophrenia. Also, understanding the molecular mechanisms of miRNAs in schizophrenia pathogenesis can pave the way for developing novel treatments for patients with schizophrenia. In this study, we reviewed the glutamatergic and dopaminergic pathophysiology and highlighted the role of miRNA dysregulation in schizophrenia development. Besides, we shed light on the significance of circulating miRNAs for schizophrenia diagnosis and the recent findings on the miRNA-based treatment for schizophrenia.

Irrespective of medical technology improvements, cancer ranks among the leading causes of mortality worldwide. Although numerous cures and treatments exist, creating alternative cancer therapies with fewer adverse side effects is vital. Since ancient times, plant bioactive compounds have already been used as a remedy to heal cancer. These plant bioactive compounds and their anticancer activity can also deregulate the microRNAs (miRNAs) in the cancerous cells. Therefore, the deregulation of miRNAs in cancer cells by plant bioactive compounds and the usage of the related miRNA could be a promising approach for cancer cure, mainly to prevent cancer and overcome chemotherapeutic side effect problems. Hence, this review highlights the function of plant bioactive compounds as an anticancer agent through the underlying mechanism that alters the miRNA expression in cancer cells, ultimately leading to apoptosis. Moreover, this review provides insight into using plant bioactive compounds -driven miRNAs as an anticancer agent to develop miRNA-based cancer gene therapy. They can be the potential resource for gene therapy and novel strategies targeting cancer therapeutics.

Patients who suffer from sepsis typically experience acute lung injury (ALI). Extracellular vesicles (EVs) contain miRNAs, which are potentially involved in ALI. However, strategies to screen more effective EV-miRNAs as therapeutic targets are yet to be elucidated. In this study, functional EV-miRNAs were identified based on multiomics analysis of single-cell RNA sequencing of targeted organs and serum EV (sEV) miRNA profiles in patients with sepsis. The proportions of neutrophils and macrophages were increased significantly in the lungs of mice receiving sEVs from patients with sepsis compared with healthy controls. Macrophages released more EVs than neutrophils. MiR-125a-5p delivery by sEVs to lung macrophages inhibited Tnfaip3, while miR-221-3p delivery to lung neutrophils inhibited Fos. Macrophage membrane nanoparticles (MM NPs) loaded with an miR-125a-5p inhibitor or miR-221-3p mimic attenuated the response to lipopolysaccharide (LPS)-induced ALI. Transcriptome profiling revealed that EVs derived from LPS-stimulated bone marrow-derived macrophages (BMDMs) induced oxidative stress in neutrophils. Blocking toll-like receptor, CXCR2, or TNFα signaling in neutrophils attenuated the oxidative stress induced by LPS-stimulated BMDM-EVs. This study presents a novel method to screen functional EV-miRNAs and highlights the pivotal role of macrophage-derived EVs in ALI. MM NPs, as delivery systems of key sEV-miRNA mimics or inhibitors, alleviated cellular responses observed in sepsis-induced ALI. This strategy can be used to reduce septic organ damage, particularly lung damage, by targeting EVs.

Nonalcoholic steatohepatitis (NASH) represents a severe disease subtype of nonalcoholic fatty liver disease (NAFLD) that is thought to be highly associated with systemic metabolic abnormalities. It is characterized by a series of substantial liver damage, including hepatocellular steatosis, inflammation, and fibrosis. The end stage of NASH, in some cases, may result in cirrhosis and hepatocellular carcinoma (HCC). Nowadays a large number of investigations are actively under way to test various therapeutic strategies, including emerging oligonucleotide drugs (e.g., antisense oligonucleotide, small interfering RNA, microRNA, mimic/inhibitor RNA, and small activating RNA) that have shown high potential in treating this fatal liver disease. This article systematically reviews the pathogenesis of NASH/NAFLD, the promising druggable targets proven by current studies in chemical compounds or biological drug development, and the feasibility and limitations of oligonucleotide-based therapeutic approaches under clinical or pre-clinical studies.

Stroke represents one of the neurological diseases most responsible for death and permanent disability in the world. Different factors, such as thrombus, emboli and atherosclerosis, take part in the intricate pathophysiology of stroke. Comprehending the molecular processes involved in this mechanism is crucial to developing new, specific and efficient treatments. Some common mechanisms are excitotoxicity and calcium overload, oxidative stress and neuroinflammation. Furthermore, non-coding RNAs (ncRNAs) are critical in pathophysiology and recovery after cerebral ischemia. ncRNAs, particularly microRNAs, and long non-coding RNAs (lncRNAs) are essential for angiogenesis and neuroprotection, and they have been suggested to be therapeutic, diagnostic and prognostic tools in cerebrovascular diseases, including stroke. This review summarizes the intricate molecular mechanisms underlying ischemic and hemorrhagic stroke and delves into the function of miRNAs in the development of brain damage. Furthermore, we will analyze new perspectives on treatment based on molecular mechanisms in addition to traditional stroke therapies.

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most common inherited kidney condition caused by a single-gene mutation. It leads patients to kidney failure in more than 50% of cases by the age of 60, and, given the dominant inheritance, this disease is present in the family history in more than 90% of cases.

This review aims to analyze the set of preclinical and early-phase studies to provide a general view of the current progress on ADPKD therapeutic options. Articles from PubMed and the current status of the trials listed in clinicaltrials.gov were examined for the review.

Many potential therapeutic targets are currently under study for the treatment of ADPKD. A few drugs have reached the clinical phase, while many are currently still in the preclinical phase. Organoids could be a novel approach to the study of drugs in this phase. Other than pharmacological options, very important developing approaches are represented by gene therapy and the use of MiRNA inhibitors.

Afamin is a hepatokine that involves in glucose and lipids metabolism. miR-122 is mainly expressed in liver and involves in lipid and carbohydrate metabolism. This study aimed at investigating the circulating afamin, its correlation with type 2 diabetes mellitus (T2DM) and miR-122 gene expression in T2DM patients and healthy control subjects according to the duration of diabetes.

This case-control study included 220 participants, with 100 individuals serving as controls and 120 individuals diagnosed with type 2 diabetes mellitus (T2DM). The miR-122 gene expression was assessed using real-time PCR. The serum concentration of biochemical parameters such as glucose levels, lipid profile, and small-dense low-density lipoprotein (sdLDL) were measured using colorimetric kits. Circulating afamin and insulin levels were assayed using an ELISA kit. Glycated hemoglobin (HbA1c) was measured using capillary electrophoresis.

Circulating afamin level was significantly higher in T2DM patients compared to the control group, (73.8 ± 10.8 vs. 65.9 ± 8.7, respectively; P < 0.001). Similarly, miR122 expression was significantly increased in T2DM patients compared to healthy control subjects (4.24 ± 2.01 vs. 1.00 ± 0.85, respectively; P < 0.001). Among patients diagnosed with T2DM, those with longstanding diabetes (>5 years) exhibited significantly higher levels of circulating afamin and miR-122 expression compared to individuals with a shorter duration of diabetes (≤5 years) (P < 0.05). Circulating afamin levels were significantly correlated with waist circumference, small-dense low-density lipoprotein (sdLDL), fasting blood sugar (FBS), insulin, resistance to insulin, and miR-122 expression, depending on the duration of the disease (P < 0.05). Furthermore, the performance of afamin as a diagnostic marker for T2DM was confirmed through receiver operating characteristic (ROC) analysis, yielding an area under the curve (AUC) of 0.7 (P < 0.001).

Circulating afamin involved in the T2DM-related complications and its concentration is positively correlated to the miR-122 expression, especially in patient with longstanding diabetes.

Antisense oligonucleotides (ASOs) are widely used as therapeutics for neurodegenerative diseases, cancers, and virus infections. One class of ASOs functions to enhance protein expression by sequestering the mature microRNA (miRNA) in a double-stranded structure within the RNA-induced silencing complex (RISC). An alternative approach for the targeted control of gene expression is to use ASOs that bind to the pre-elements of miRNAs (pre-miRNAs) and modulate their enzymatic processing. Here, we demonstrate that ASOs can be used to disrupt a specific structural feature, "junction," within pre-miR-31 that is important in directing efficient processing by the Dicer/TRBP complex. Furthermore, we extend and validate this strategy to pre-miR-144, which has a similar junction-dependent structure-function relationship. We found that a significant number of human pre-miRNAs are predicted to contain junctions, and validated our ASO approach on several members of this group. Importantly, we also verified the application of junction-targeting ASOs for the specific inhibition of pre-miRNA processing in cell. Our study reemphasizes the important roles of RNA structure in regulating Dicer/TRBP processing of pre-miRNAs and provides the framework to develop structure-informed ASOs that serve to inhibit miRNA production.

Physiological cardiac hypertrophy occurs in response to exercise and can protect against pathological stress. In contrast, pathological hypertrophy occurs in disease and often precedes heart failure. The cardiac pathways activated in physiological and pathological hypertrophy are largely distinct. Our prior work demonstrated that miR-222 increases in exercised hearts and is required for exercise-induced cardiac hypertrophy and cardiomyogenesis. Here, we sought to define the role of miR-222 in pathological hypertrophy.

We found that miR-222 also increased in pathological hypertrophy induced by pressure overload. To assess its functional significance in this setting, we generated a miR-222 gain-of-function model through cardiac-specific constitutive transgenic miR-222 expression (TgC-miR-222) and used locked nucleic acid anti-miR specific for miR-222 to inhibit its effects. Both gain- and loss-of-function models manifested normal cardiac structure and function at baseline. However, after transverse aortic constriction (TAC), miR-222 inhibition accelerated the development of pathological hypertrophy, cardiac dysfunction, and heart failure. Conversely, miR-222-overexpressing mice had less pathological hypertrophy after TAC, as well as better cardiac function and survival. We identified p53-up-regulated modulator of apoptosis, a pro-apoptotic Bcl-2 family member, and the transcription factors, Hmbox1 and nuclear factor of activated T-cells 3, as direct miR-222 targets contributing to its roles in this context.

While miR-222 is necessary for physiological cardiac growth, it inhibits cardiac growth in response to pressure overload and reduces adverse remodelling and cardiac dysfunction. These findings support the model that physiological and pathological hypertrophy are fundamentally different. Further, they suggest that miR-222 may hold promise as a therapeutic target in pathological cardiac hypertrophy and heart failure.

Depression is a major contributor to the overall global burden of disease. The discovery of biomarkers for diagnosis or prediction of treatment responses and as therapeutic agents is a current priority. Previous studies have demonstrated the importance of short RNA molecules in the etiology of depression. The most extensively researched of these are microRNAs, a major component of cellular gene regulation and function. MicroRNAs function in a temporal and tissue-specific manner to regulate and modify the post-transcriptional expression of target mRNAs. They can also be shuttled as cargo of extracellular vesicles between the brain and the blood, thus informing about relevant mechanisms in the CNS through the periphery. In fact, studies have already shown that microRNAs identified peripherally are dysregulated in the pathological phenotypes seen in depression. Our article aims to review the existing evidence on microRNA dysregulation in depression and to summarize and evaluate the growing body of evidence for the use of microRNAs as a target for diagnostics and RNA-based therapies.

The incidence of hepatocellular carcinoma (HCC) is increasing, and 40% of patients are diagnosed at advanced stages. Over the past 5 years, the number of clinically available treatments has dramatically increased for HCC, making patient management particularly complex. Immune checkpoint inhibitors (ICIs) have improved the overall survival of patients, showing a durable treatment benefit over time and a different response pattern with respect to tyrosine kinase inhibitors (TKIs). Although there is improved survival in responder cases, a sizeable group of patients are primary progressors or are ineligible for immunotherapy. Indeed, patients with nonviral etiologies, such as nonalcoholic steatohepatitis (NASH), and alterations in specific driver genes might be less responsive to immunotherapy. Therefore, improving the comprehension of mechanisms of drug resistance and identifying biomarkers that are informative of the best treatment approach are required actions to improve patient survival. Abundant evidence indicates that noncoding RNAs (ncRNAs) are pivotal players in cancer. Molecular mechanisms through which ncRNAs exert their effects in cancer progression and drug resistance have been widely investigated. Nevertheless, there are no studies summarizing the synergistic effect between ncRNA-based strategies and TKIs or ICIs in the preclinical setting. This review aims to provide up-to-date information regarding the possible use of ncRNAs as therapeutic targets in association with molecular-targeted agents and immunotherapies and as predictive tools for the selection of optimized treatment options in advanced HCCs.

Diabetic retinopathy (DR) is a severe microvascular complication of diabetes and is one of the primary causes of blindness in the working-age population in Europe and the United States. At present, no cure is available for DR, but early detection and timely intervention can prevent the rapid progression of the disease. Several treatments for DR are known, primarily ophthalmic treatment based on glycemia, blood pressure, and lipid control, which includes laser photocoagulation, glucocorticoids, vitrectomy, and antivascular endothelial growth factor (anti-VEGF) medications. Despite the clinical efficacy of the aforementioned therapies, none of them can entirely shorten the clinical course of DR or reverse retinopathy. MicroRNAs (miRNAs) are vital regulators of gene expression and participate in cell growth, differentiation, development, and apoptosis. MicroRNAs have been shown to play a significant role in DR, particularly in the molecular mechanisms of inflammation, oxidative stress, and neurodegeneration. The aim of this review is to systematically summarize the signaling pathways and molecular mechanisms of miRNAs involved in the occurrence and development of DR, mainly from the pathogenesis of oxidative stress, inflammation, and neovascularization. Meanwhile, this article also discusses the research progress and application of miRNA-specific therapies for DR.

The discovery of the link between microRNAs (miRNAs) and a myriad of human diseases, particularly various cancer types, has generated significant interest in exploring their potential as a novel class of drugs. This has led to substantial investments in interdisciplinary research fields such as biology, chemistry, and medical science for the development of miRNA-based therapies. Furthermore, the recent global success of SARS-CoV-2 mRNA vaccines against the COVID-19 pandemic has further revitalized interest in RNA-based immunotherapies, including miRNA-based approaches to cancer treatment. Consequently, RNA therapeutics have emerged as highly adaptable and modular options for cancer therapy. Moreover, advancements in RNA chemistry and delivery methods have been pivotal in shaping the landscape of RNA-based immunotherapy, including miRNA-based approaches. Consequently, the biotechnology and pharmaceutical industry has witnessed a resurgence of interest in incorporating RNA-based immunotherapies and miRNA therapeutics into their development programs. Despite substantial progress in preclinical research, the field of miRNA-based therapeutics remains in its early stages, with only a few progressing to clinical development, none reaching phase III clinical trials or being approved by the US Food and Drug Administration (FDA), and several facing termination due to toxicity issues. These setbacks highlight existing challenges that must be addressed for the broad clinical application of miRNA-based therapeutics. Key challenges include establishing miRNA sensitivity, specificity, and selectivity towards their intended targets, mitigating immunogenic reactions and off-target effects, developing enhanced methods for targeted delivery, and determining optimal dosing for therapeutic efficacy while minimizing side effects. Additionally, the limited understanding of the precise functions of miRNAs limits their clinical utilization. Moreover, for miRNAs to be viable for cancer treatment, they must be technically and economically feasible for the widespread adoption of RNA therapies. As a result, a thorough risk evaluation of miRNA therapeutics is crucial to minimize off-target effects, prevent overdosing, and address various other issues. Nevertheless, the therapeutic potential of miRNAs for various diseases is evident, and future investigations are essential to determine their applicability in clinical settings.

Recently, we found DNA/RNA heteroduplex oligonucleotide-based antimiR (HDO-antimiR) can more efficiently inhibit the target miRNA than conventional antimiR after its cellular uptake. But the mechanism of HDO-antimiR about the target-silencing is unknown. We here tried to elucidate the interaction mechanism of HDO-antimiR to miRNA using molecular dynamics (MD) simulation. When interaction of the conventional antimiR or HDO-antimiR and the target miRNA was simulated, they combined with each other in various forms. In the hydrogen bond analyses, base site of the antimiR formed hydrogen bond with miRNA. On the other hand, phosphate site of the HDO-antimiR formed hydrogen bond with miRNA. These results suggested that there were differences about the binding mechanisms between antimiR and HDO-antimiR to the target miRNA. In particular, there was a difference in the binding site between antimiR and HDO-antimiR. Additionally, it was found that guanine in the miRNA is mainly involved in the binding to the antimiR or HDO-antimiR. MD simulation method is useful in understanding the mechanism of oligonucleotide therapeutics.

Vanin1 (VNN1) is an exogenous enzyme with pantetheinase activity that mainly exerts physiological functions through enzyme catalysis products, including pantothenic acid and cysteamine. In recent years, the crosstalk between VNN1 and metabolism and oxidative stress has attracted much attention. As a result of the ability of VNN1 to affect multiple metabolic pathways and oxidative stress to exacerbate or alleviate pathological processes, it has become a key component of disease progression. This review discusses the functions of VNN1 in glucolipid metabolism, cysteamine metabolism, and glutathione metabolism to provide perspectives on VNN1-targeted therapy for chronic diseases.

Gamma peptide nucleic acids (γPNAs) have recently garnered attention in diverse therapeutic and diagnostic applications. Serine and diethylene-glycol-containing γPNAs have been tested for numerous RNA-targeting purposes. Here, we comprehensively evaluated the in vitro and in vivo efficacy of pH-low insertion peptide (pHLIP)-conjugated serine and diethylene-based γPNAs. pHLIP targets only the acidic tumor microenvironment and not the normal cells. We synthesized and parallelly tested pHLIP-serine γPNAs and pHLIP-diethylene glycol γPNAs that target the seed region of microRNA-155, a microRNA that is upregulated in various cancers. We performed an all-atom molecular dynamics simulation-based computational study to elucidate the interaction of pHLIP-γPNA constructs with the lipid bilayer. We also determined the biodistribution and efficacy of the pHLIP constructs in the U2932-derived xenograft model. Overall, we established that the pHLIP-serine γPNAs show superior results in vivo compared with the pHLIP-diethylene glycol-based γPNA.

microRNA-122 (miR-122) is a highly conserved microRNA that is predominantly expressed in the liver and plays a critical role in the regulation of liver metabolism. Recent studies have shown that miR-122 is involved in the pathogenesis of various types of cancer, particularly liver cancer. In this sense, The current findings highlighted the potential role of miR-122 in regulating many vital processes in cancer pathophysiology, including apoptosis, signaling pathway, cell metabolism, immune system response, migration, and invasion. These results imply that miR-122, which has been extensively studied for its biological functions and potential therapeutic applications, acts as a tumor suppressor or oncogene in cancer development. We first provide an overview and summary of the physiological function and mode of action of miR-122 in liver cancer. We will examine the various signaling pathways and molecular mechanisms through which miR-122 exerts its effects on cancer cells, including the regulation of oncogenic and tumor suppressor genes, the modulation of cell proliferation and apoptosis, and the regulation of metastasis. Most importantly, we will also discuss the potential diagnostic and therapeutic applications of miR-122 in cancer, including the development of miRNA-based biomarkers for cancer diagnosis and prognosis, and the potential use of miR-122 as a therapeutic target for cancer treatment.

MicroRNAs are attractive therapeutic targets in many diseases, including chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis. Among microRNA inhibitors antimiRs have been proven successful in lowering aberrant microRNA levels in the clinic. We present a set of antimiRs targeting miR-34a, which has been shown to be dysregulated in chronic lung diseases. The tool compounds were taken up by a bronchial epithelial cell line and primary human bronchial epithelial cells, followed by efficient knockdown of miR-34a. Similar results were observed in 3D differentiated primary human bronchial epithelial cells cultured at the air-liquid interface. Varying chemical properties of antimiRs had significant impact on cellular uptake and potency, resulting in effective tool compounds for use in lung-relevant cellular systems. This report demonstrates gymnotic antimiR uptake and activity in 3D epithelial cell culture after apical administration, mimicking inhalation conditions.

microRNAs (miRNAs) are small, non-coding RNA molecules that play crucial regulatory roles in numerous cellular processes. Recent investigations have highlighted the significant involvement of miRNA-122 (miR-122) in the pathogenesis of infectious diseases caused by diverse pathogens, encompassing viral, bacterial, and parasitic infections. In the context of viral infections, miR-122 exerts regulatory control over viral replication by binding to the viral genome and modulating the host's antiviral response. For instance, in hepatitis B virus (HBV) infection, miR-122 restricts viral replication, while HBV, in turn, suppresses miR-122 expression. Conversely, miR-122 interacts with the hepatitis C virus (HCV) genome, facilitating viral replication. Regarding bacterial infections, miR-122 has been found to regulate host immune responses by influencing inflammatory cytokine production and phagocytosis. In Vibrio anguillarum infections, there is a significant reduction in miR-122 expression, contributing to the pathophysiology of bacterial infections. Toll-like receptor 14 (TLR14) has been identified as a novel target gene of miR-122, affecting inflammatory and immune responses. In the context of parasitic infections, miR-122 plays a crucial role in regulating host lipid metabolism and immune responses. For example, during Leishmania infection, miR-122-containing extracellular vesicles from liver cells are unable to enter infected macrophages, leading to a suppression of the inflammatory response. Furthermore, miR-122 exhibits promise as a potential biomarker for various infectious diseases. Its expression level in body fluids, particularly in serum and plasma, correlates with disease severity and treatment response in patients affected by HCV, HBV, and tuberculosis. This paper also discusses the potential of miR-122 as a biomarker in infectious diseases. In summary, this review provides a comprehensive and insightful overview of the emerging role of miR-122 in infectious diseases, detailing its mechanism of action and potential implications for the development of novel therapeutic strategies.

Merkel cell carcinoma (MCC) is an uncommon invasive form of skin cancer that typically manifests as a nodule on the face, head, or neck that is flesh-colored or bluish-red in appearance. Rapid growth and metastasis are hallmarks of MCC. MCC has the second-greatest mortality rate among skin cancers after melanoma. Despite the recent cascade of molecular investigations, no universal molecular signature has been identified as responsible for MCC's pathogenesis. The microRNAs (miRNAs) play a critical role in the post-transcriptional regulation of gene expression. Variations in the expression of these short, non-coding RNAs have been associated with various malignancies, including MCC. Although the incidence of MCC is very low, a significant amount of study has focused on the interaction of miRNAs in MCC. As such, the current survey is a speedy intensive route revealing the potential involvement of miRNAs in the pathogenesis of MCC beyond their association with survival in MCC.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for COVID-19, utilizes receptor binding domain (RBD) of spike glycoprotein to interact with angiotensin (Ang)-converting enzyme 2 (ACE2). Altering ACE2 levels may affect entry of SARS-CoV-2 and recovery from COVID-19. Decreased cell surface density of ACE2 leads to increased local levels of Ang II and may contribute to mortality resulting from acute lung injury and fibrosis during COVID-19. Studies published early during the COVID-19 pandemic reported that people with cystic fibrosis (PwCF) had milder symptoms, compared to people without CF. This finding was attributed to elevated ACE2 levels and/or treatment with the high efficiency CFTR modulators. Subsequent studies did not confirm these findings reporting variable effects of CFTR gene mutations on ACE2 levels. Transforming growth factor (TGF)-β signaling is essential during SARS-CoV-2 infection and dominates the chronic immune response in severe COVID-19, leading to pulmonary fibrosis. TGF-β1 is a gene modifier associated with more severe lung disease in PwCF but its effects on the COVID-19 course in PwCF is unknown. To understand whether TGF-β1 affects ACE2 levels in the airway, we examined miRNAs and their gene targets affecting SARS-CoV-2 pathogenesis in response to TGF-β1. Small RNAseq and micro(mi)RNA profiling identified pathways uniquely affected by TGF-β1, including those associated with SARS-CoV-2 invasion, replication, and the host immune responses. TGF-β1 inhibited ACE2 expression by miR-136-3p and miR-369-5p mediated mechanism in CF and non-CF bronchial epithelial cells. ACE2 levels were higher in two bronchial epithelial cell models expressing the most common CF-causing mutation in CFTR gene F508del, compared to controls without the mutation. After TGF-β1 treatment, ACE2 protein levels were still higher in CF, compared to non-CF cells. TGF-β1 prevented the modulator-mediated rescue of F508del-CFTR function while the modulators did not prevent the TGF-β1 inhibition of ACE2 levels. Finally, TGF-β1 reduced the interaction between ACE2 and the recombinant spike RBD by lowering ACE2 levels and its binding to RBD. Our data demonstrate novel mechanism whereby TGF-β1 inhibition of ACE2 in CF and non-CF bronchial epithelial cells may modulate SARS-CoV-2 pathogenicity and COVID-19 severity. By reducing ACE2 levels, TGF-β1 may decrease entry of SARS-CoV-2 into the host cells while hindering the recovery from COVID-19 due to loss of the anti-inflammatory and regenerative effects of ACE2. The above outcomes may be modulated by other, miRNA-mediated effects exerted by TGF-β1 on the host immune responses, leading to a complex and yet incompletely understood circuitry.

microRNAs (miRNAs) play a crucial role in various biological processes, including immune system regulation, such as cell proliferation, tolerance (central and peripheral), and T helper cell development. Dysregulation of miRNA expression and activity can disrupt immune responses and increase susceptibility to neuroimmune disorders. Conversely, miRNAs have been shown to have a protective role in modulating immune responses and preventing autoimmunity. Specifically, reducing the expression of miRNA-128 (miR-128) in an Alzheimer's disease (AD) mouse model has been found to improve cognitive deficits and reduce neuropathology. This comprehensive review focuses on the significance of miR-128 in the pathogenesis of neuroautoimmune disorders, including multiple sclerosis (MS), AD, Parkinson's disease (PD), Huntington's disease (HD), epilepsy, as well as other immune-mediated diseases such as inflammatory bowel disease (IBD) and rheumatoid arthritis (RA). Additionally, we present compelling evidence supporting the potential use of miR-128 as a diagnostic or therapeutic biomarker for neuroimmune disorders. Collectively, the available literature suggests that targeting miR-128 could be a promising strategy to alleviate the behavioral symptoms associated with neuroimmune diseases. Furthermore, further research in this area may uncover new insights into the molecular mechanisms underlying these disorders and potentially lead to the development of novel therapeutic approaches.

Pyroptosis is a type of programmed cell death that induces myocardial ischemia-reperfusion injury (I/RI), which leads to cardiac dysfunction and even lethal reperfusion injury. MiR-122 is a liver-specific miRNA associated with coronary heart disease, but its role in pyroptosis activation in myocardial I/RI remains unclear. Thus, this study aimed to determine whether miR-122 inhibition exerts myocardial I/RI protection in in vivo and in vitro models. An I/RI model was established in vivo using C57BL/J6 male mice. MiR-122 expression was upregulated in the heart tissues from the I/RI group. Quantitative results of echocardiography parameters showed that miR-122 inhibition improved cardiac function and downregulated interleukin (IL)-1β, IL-18, caspase 1, and caspase 11. However, pretransfection with recombinant adeno-associated virus type 9 encoding a DUSP4-specific siRNA (AAV9-siDUSP4) blocked the protective effects of miR-122 inhibition. A hypoxia/reoxygenation (H/R) model was established to mimic the I/R condition in vitro using H9C2 cells. Results showed that miR-122 inhibition increased superoxide dismutase activity (SOD) and cell viability and decreased malondialdehyde (MDA) level, IL-1β, IL-18, caspase 1, caspase 11, and cell death. These protective effects were abolished by transfection with DUSP4-specific siRNA. In summary, miR-122 expression is upregulated in I/RI, and miR-122 inhibition alleviates I/RI by suppressing pyroptosis through targeting DUSP4. Thus, miR-122 may be a novel therapeutic target for treating myocardial I/RI.

The long non-coding RNAs (lncRNAs) constitute an important class of the human transcriptome. The discovery of lncRNAs provided one of many unexpected results of the post-genomic era and uncovered a huge number of previously ignored transcriptional events. In recent years, lncRNAs are known to be linked with human diseases, with particular focus on cancer. Growing evidence has indicated that dysregulation of lncRNAs in breast cancer (BC) is strongly associated with the occurrence, development, and progress. Increasing numbers of lncRNAs have been found to interact with cell cycle progression and tumorigenesis in BC. The lncRNAs can exert their effect as a tumor suppressor or oncogene and regulate tumor development through direct or indirect regulation of cancer-related modulators and signaling pathways. What is more, lncRNAs are excellent candidates for promising therapeutic targets in BC due to the features of high tissue and cell-type specific expression. However, the underlying mechanisms of lncRNAs in BC still remain largely undefined. Here, we concisely summarize and sort out the current understanding of research progress in relationships of the roles for lncRNA in regulating the cell cycle. We also summarize the evidence for aberrant lncRNA expression in BC, and the potential for lncRNA to improve BC therapy is also discussed. Together, lncRNAs can be considered as exciting therapeutic candidates whose expression can be altered to impede BC progression.

MicroRNAs (miRNAs) play a critical role in the regulation of mRNA stability and translation. In spite of our present knowledge on the mechanisms of mRNA regulation by miRNAs, the utilization and translation of these ncRNAs into clinical applications have been problematic. Using hsa-miR-429 as an example, we discuss the limitations encountered in the development of efficient miRNA-related therapies and diagnostic approaches. The miR-200 family members, which include hsa-miR-429, have been shown to be dysregulated in different types of cancer. Although these miR-200 family members have been shown to function in suppressing epithelial-to-mesenchymal transition, tumor metastasis, and chemoresistance, the experimental results have often been contradictory. These complications involve not only the complex networks involving these noncoding RNAs, but also the problem of identifying false positives. To overcome these limitations, a more comprehensive research strategy is needed to increase our understanding of the mechanisms underlying their biological role in mRNA regulation. Here, we provide a literature analysis of the verified hsa-miR-429 targets in various human research models. A meta-analysis of this work is presented to provide better insights into the role of hsa-miR-429 in cancer diagnosis and any potential therapeutic approach.

Esophageal squamous cell carcinoma (ESCC) is a deadly disease with few prevention or treatment options. ESCC development in humans and rodents is associated with Zn deficiency (ZD), inflammation, and overexpression of oncogenic microRNAs: miR-31 and miR-21. In a ZD-promoted ESCC rat model with upregulation of these miRs, systemic antimiR-31 suppresses the miR-31-EGLN3/STK40-NF-κB-controlled inflammatory pathway and ESCC. In this model, systemic delivery of Zn-regulated antimiR-31, followed by antimiR-21, restored expression of tumor-suppressor proteins targeted by these specific miRs: STK40/EGLN3 (miR-31), PDCD4 (miR-21), suppressing inflammation, promoting apoptosis, and inhibiting ESCC development. Moreover, ESCC-bearing Zn-deficient (ZD) rats receiving Zn medication showed a 47% decrease in ESCC incidence vs. Zn-untreated controls. Zn treatment eliminated ESCCs by affecting a spectrum of biological processes that included downregulation of expression of the two miRs and miR-31-controlled inflammatory pathway, stimulation of miR-21-PDCD4 axis apoptosis, and reversal of the ESCC metabolome: with decrease in putrescine, increase in glucose, accompanied by downregulation of metabolite enzymes ODC and HK2. Thus, Zn treatment or miR-31/21 silencing are effective therapeutic strategies for ESCC in this rodent model and should be examined in the human counterpart exhibiting the same biological processes.

Epigenetic changes associated with disease development and progressions are of increasing importance because of their potential diagnostic and therapeutic applications. Several epigenetic changes associated with chronic metabolic disorders have been studied in various diseases. Epigenetic changes are mostly modulated by environmental factors, including the human microbiota living in different parts of our bodies. The microbial structural components and the microbially derived metabolites directly interact with host cells, thereby maintaining homeostasis. Microbiome dysbiosis, on the other hand, is known to produce elevated levels of disease-linked metabolites, which may directly affect a host metabolic pathway or induce epigenetic changes that can lead to disease development. Despite their important role in host physiology and signal transduction, there has been little research into the mechanics and pathways associated with epigenetic modifications. This chapter focuses on the relationship between microbes and their epigenetic effects in diseased pathology, as well as on the regulation and metabolism of the dietary options available to the microbes. Furthermore, this chapter also provides a prospective link between these two important phenomena, termed "Microbiome and Epigenetics."

miR-122 is a liver specific micro-RNA that participates in the regulation of carbohydrate and lipid metabolism. The rs17669 variant of miR-122 is positioned at the flanking region of miR-122 and may affect its stability and maturation. Therefore, this study was aimed to investigate the association of the rs17669 polymorphism with the miR-122 circulating level, risk of type 2 diabetes mellitus (T2DM) development, and biochemical parameters in T2DM patients and matched healthy controls.

This study involved 295 subjects (controls: n = 145 and T2DM: n = 150). The rs17669 variant genotyping was done by ARMS-PCR. Serum biochemical parameters including lipid profile, small-dense low density lipoprotein (sdLDL) and glucose were measured by colorimetric kits. Insulin and Glycated hemoglobin (HbA1c) were assayed using ELISA and capillary electrophoresis methods, respectively. miR-122 expression was measured by real-time PCR. There was no significant difference between study groups in terms of allele and genotype distribution (P > 0.05). The rs17669 variant did not have any significant association with miR-122 gene expression and biochemical parameters (P > 0.05). miR-122 expression level in T2DM patients was significantly higher than that in control subjects (5.7 ± 2.4 vs. 1.4 ± 0.78) (P < 0.001). Furthermore, miR-122 fold change had a positive and significant correlation with low-density lipoprotein cholesterol (LDL-C), sdLDL, fasting blood sugar (FBS), and insulin resistance (P < 0.05).

It can be concluded that the rs17669 variant of miR-122 is not associated with the miR-122 expression and T2DM-associated serum parameters. Furthermore, it can be suggested that miR-122 dysregulation is involved in T2DM development through inducing dyslipidemia, hyperglycemia, and resistance to insulin.

The three sets of symptoms associated with schizophrenia-positive, negative, and cognitive-are burdensome and have serious effects on public health, which affects up to 1% of the population. It is now commonly believed that in addition to the traditional dopaminergic mesolimbic pathway, the etiology of schizophrenia also includes neuronal networks, such as glutamate, GABA, serotonin, BDNF, oxidative stress, inflammation and the immune system. Small noncoding RNA molecules called microRNAs (miRNAs) have come to light as possible participants in the pathophysiology of schizophrenia in recent years by having an impact on these systems. These small RNAs regulate the stability and translation of hundreds of target transcripts, which has an impact on the entire gene network. There may be improved approaches to treat and diagnose schizophrenia if it is understood how these changes in miRNAs alter the critical related signaling pathways that drive the development and progression of the illness.

The partial remission (PR) phase of type 1 diabetes (T1D) is an underexplored period characterized by endogenous insulin production and downmodulated autoimmunity. To comprehend the mechanisms behind this transitory phase and develop precision medicine strategies, biomarker discovery and patient stratification are unmet needs. MicroRNAs (miRNAs) are small RNA molecules that negatively regulate gene expression and modulate several biological processes, functioning as biomarkers for many diseases. Here, we identify and validate a unique miRNA signature during PR in pediatric patients with T1D by employing small RNA sequencing and RT-qPCR. These miRNAs were mainly related to the immune system, metabolism, stress, and apoptosis pathways. The implication in autoimmunity of the most dysregulated miRNA, miR-30d-5p, was evaluated in vivo in the non-obese diabetic mouse. MiR-30d-5p inhibition resulted in increased regulatory T cell percentages in the pancreatic lymph nodes together with a higher expression of CD200. In the spleen, a decrease in PD-1⁺ T lymphocytes and reduced PDCD1 expression were observed. Moreover, miR-30d-5p inhibition led to an increased islet leukocytic infiltrate and changes in both effector and memory T lymphocytes. In conclusion, the miRNA signature found during PR shows new putative biomarkers and highlights the immunomodulatory role of miR-30d-5p, elucidating the processes driving this phase.

The bone marrow niche plays an increasing role in the pathophysiogenesis of myelodysplastic syndromes. More specifically, mesenchymal stromal cells, which can secrete extracellular vesicles and their miRNA contents, modulate the fate of hematopoietic stem cells leading to leukemogenesis. Extracellular vesicles can mediate their miRNA and protein contents between nearby cells but also in the plasma of the patients, being potent tools for diagnosis and prognostic markers in MDS. They can be targeted by antisense miRNA or by modulators of the secretion of extracellular vesicles and could lead to future therapeutic directions in MDS.

It has been demonstrated that noncoding RNAs have significant physiological and pathological roles. Modulation of noncoding RNAs may offer therapeutic approaches as per recent findings. Small RNAs, mostly long noncoding RNAs, siRNA, and microRNAs make up noncoding RNAs. Inhibiting or promoting protein breakdown by binding to 3' untranslated regions of target mRNA, microRNAs post-transcriptionally control the pattern of gene expression. Contrarily, long non-coding RNAs perform a wider range of tasks, including serving as molecular scaffolding, decoys, and epigenetic regulators. This article provides instances of long noncoding RNAs and microRNAs that may be a biomarker of CVD (cardiovascular disease). In this paper we highlight various RNA-based vaccine formulation strategies designed to target these biomarkers-that are either currently in the research pipeline or are in the global pharmaceutical market-along with the physiological hurdles that need to be overcome.

Endometriosis, a benign gynecologic and chronic inflammatory disease, is defined by the presence of endometrial tissue outside the uterus characterized mainly by pelvic pain and infertility. Because endometriosis affects approximately 10% of females, it represents a significant socioeconomic burden worldwide having tremendous impact on daily quality of life. Accurate and prompt diagnosis is crucial for the management of this debilitating disorder. Unfortunately, diagnosis is typically delayed to lack of specific symptoms and readily accessible biomarkers. Although histopathologic examination remains the current gold standard, this approach is highly invasive and not applicable for early screening. Recent work has focused on the identification of reliable biomarkers including immunologic, ie, immune cells, antibodies and cytokines, as well as genetic and biochemical markers, ie, microRNAs, lncRNAs, circulating and mitochondrial nucleic acids, along with some hormones, glycoproteins and signaling molecules. Confirmatory research studies are, however, needed to more fully establish these markers in the diagnosis, progression and staging of these endometrial lesions.

The aberrant increase in cardio-metabolic diseases over the past couple of decades has drawn researchers' attention to explore and unveil the novel mechanisms implicated in cardiometabolic diseases. Recent evidence disclosed that the derangement of cardiac energy substrate metabolism plays a predominant role in the development and progression of chronic cardiometabolic diseases. Hence, in-depth comprehension of the novel molecular mechanisms behind impaired cardiac metabolism-mediated diseases is crucial to expand treatment strategies. The complex and dynamic pathways of cardiac metabolism are systematically controlled by the novel executor, microRNAs (miRNAs). miRNAs regulate target gene expression by either mRNA degradation or translational repression through base pairing between miRNA and the target transcript, precisely at the 3' seed sequence and conserved heptametrical sequence in the 5' end, respectively. Multiple miRNAs are involved throughout every cardiac energy substrate metabolism and play a differential role based on the variety of target transcripts. Novel theoretical strategies have even entered the clinical phase for treating cardiometabolic diseases, but experimental evidence remains inadequate. In this review, we identify the potent miRNAs, their direct target transcripts, and discuss the remodeling of cardiac metabolism to cast light on further clinical studies and further the expansion of novel therapeutic strategies. This review is categorized into four sections which encompass (i) a review of the fundamental mechanism of cardiac metabolism, (ii) a divulgence of the regulatory role of specific miRNAs on cardiac metabolic pathways, (iii) an understanding of the association between miRNA and impaired cardiac metabolism, and (iv) summary of available miRNA targeting therapeutic approaches.

Originally discovered by Nielsen in 1991, peptide nucleic acids and other artificial genetic polymers have gained a lot of interest from the scientific community. Due to their unique biophysical features these artificial hybrid polymers are now being employed in various areas of theranostics (therapy and diagnostics). The current review provides an overview of their structure, principles of rational design, and biophysical features as well as highlights the areas of their successful implementation in biology and biomedicine. Finally, the review discusses the areas of improvement that would allow their use as a new class of therapeutics in the future.

microRNAs (miRNAs) are a class of non-coding RNAs playing a myriad of important roles in regulating gene expression. Of note, recent work demonstrated a critical role of miRNAs in the genesis and progression of brain arteriovenous malformations (bAVMs). Accordingly, here we examine miRNA signatures related to bAVMs and associated gene expression. In so doing we expound on the potential prognostic, diagnostic, and therapeutic significance of miRNAs in the clinical management of bAVMs.

A PRISMA-based literature review was performed using PubMed/Medline database with the following search terms: "brain arteriovenous malformations", "cerebral arteriovenous malformations", "microRNA", and "miRNA". All preclinical and clinical studies written in English, regardless of date, were selected. For our bioinformatic analyses, miRWalk and miRTarBase machine learning algorithms were employed; the Kyoto Encyclopedia of Genes and Genomes (KEGG) database was quired for associated pathways/functions.

four studies were ultimately included in the final analyses. Sequencing data consistently revealed the decreased expression of miR-18a in bAVM-endothelial cells, resulting in increased levels of vascular endodermal growth factor (VEGF), Id-1, matrix metalloproteinase, and growth signals. Our analyses also suggest that the downregulation of miR-137 and miR-195* within vascular smooth muscle cells (VSMCs) may foster the activation of inflammation, aberrant angiogenesis, and phenotypic switching. In the peripheral blood, the overexpression of miR-7-5p, miR-629-5p, miR-199a-5p, miR-200b-3p, and let-7b-5p may contribute to endothelial proliferation and nidus development. The machine learning algorithms employed confirmed associations between miRNA-related target networks, vascular rearrangement, and bAVM progression.

miRNAs expression appears to be critical in managing bAVMs' post-transcriptional signals. Targets of microRNAs regulate canonical vascular proliferation and reshaping. Although additional scientific evidence is needed, the identification of bAVM miRNA signatures may facilitate the development of novel prognostic/diagnostic tools and molecular therapies for bAVMs.

Novel bio-therapeutic agents that harness the properties of small, non-coding nucleic acids hold great promise for clinical applications. These include antisense oligonucleotides that inhibit messenger RNAs, microRNAs (miRNAs), or long non-coding RNAs; positive effectors of the miRNA pathway (short interfering RNAs and miRNA mimics); or small RNAs that target proteins (i.e. aptamers). These new therapies also offer exciting opportunities for cardiovascular diseases and promise to move the field towards more precise approaches based on disease mechanisms. There have been substantial advances in developing chemical modifications to improve the in vivo pharmacological properties of antisense oligonucleotides and reduce their immunogenicity. Carrier methods (e.g. RNA conjugates, polymers, and lipoplexes) that enhance cellular uptake of RNA therapeutics and stability against degradation by intracellular nucleases are also transforming the field. A number of small non-coding RNA therapies for cardiovascular indications are now approved. Moreover, there is a large pipeline of therapies in clinical development and an even larger list of putative therapies emerging from pre-clinical studies. Progress in this area is reviewed herein along with the hurdles that need to be overcome to allow a broader clinical translation.

Cardiovascular disease is the leading cause of death worldwide, outpacing pulmonary disease, infectious disease, and all forms of cancer. Myocardial infarction (MI) dominates cardiovascular disease, contributing to four out of five cardiovascular related deaths. Following MI, patients suffer adverse and irreversible myocardial remodeling associated with cardiomyocyte loss and infiltration of fibrotic scar tissue. Current therapies following MI only mitigate the cardiac physiological decline rather than restore damaged myocardium function. Direct cardiac reprogramming is one strategy that has promise in repairing injured cardiac tissue by generating new, functional cardiomyocytes from cardiac fibroblasts (CFs). With the ectopic expression of transcription factors, microRNAs, and small molecules, CFs can be reprogrammed into cardiomyocyte-like cells (iCMs) that display molecular signatures, structures, and contraction abilities similar to endogenous cardiomyocytes. The in vivo induction of iCMs following MI leads to significant reduction in fibrotic cardiac remodeling and improved heart function, indicating reprogramming is a viable option for repairing damaged heart tissue. Recent work has illustrated different methods to understand the mechanisms driving reprogramming, in an effort to improve the efficiency of iCM generation and create an approach translational into clinic. This review will provide an overview of CFs and describe different in vivo reprogramming methods.

MicroRNAs (miRNAs) are short, non-protein-coding genes that regulate the expression of numerous protein-coding genes. Their expression is dysregulated in cancer, where they may function as oncogenes or tumour suppressor genes. As miRNAs are highly resistant to degradation, they are ideal biomarker candidates to improve the diagnosis and clinical management of cancer, including prognostication. Furthermore, miRNAs dysregulated in malignancy represent potential therapeutic targets. The use of miRNAs for these purposes is a particularly attractive option to explore for paediatric malignancies, where the mutational burden is typically low, in contrast to cancers affecting adult patients. As childhood cancers are rare, it has taken time to accumulate the necessary body of evidence showing the potential for miRNAs to improve clinical management across this group of tumours. Here, we review the current literature regarding the potential clinical utility of miRNAs in paediatric solid tumours, which is now both timely and justified. Exploring such avenues is warranted to improve the management and outcomes of children affected by cancer.

Obesity and type 2 diabetes are major contributors to the growing prevalence of non-alcoholic fatty liver disease (NAFLD), a chronic liver condition characterized by the accumulation of fat in individuals without a significant amount of alcohol intake. The NAFLD spectrum ranges from simple steatosis (early stages, known as NAFL) to non-alcoholic steatohepatitis, which can progress to fibrosis and cirrhosis or hepatocellular carcinoma. Obesity, type 2 diabetes and NAFLD are strongly associated with insulin resistance. In the liver, insulin resistance increases hepatic glucose output, lipogenesis and very-low-density lipoprotein secretion, leading to a combination of hyperglycemia and hypertriglyceridemia. Aberrant gene expression is a hallmark of insulin resistance. Non-coding RNAs (ncRNAs) have emerged as prominent regulators of gene expression that operate at the transcriptional, post-transcriptional and post-translational levels. In the last couple of decades, a wealth of studies have provided evidence that most processes of liver metabolism are orchestrated by ncRNAs. This review focuses on the role of microRNAs, long non-coding RNAs and circular RNAs as coordinators of hepatic function, as well as the current understanding on how their dysregulation contributes to abnormal metabolism and pathophysiology in animal models of insulin resistance and NAFLD. Moreover, ncRNAs are emerging as useful biomarkers that may be able to discriminate between the different stages of NAFLD. The potential of ncRNAs as therapeutic drugs for NAFLD treatment and as biomarkers is discussed.

MicroRNAs (miRNAs) are non-coding RNAs which modulate gene expression via multiple post-transcriptional mechanisms. They are involved in a variety of biological processes, including cell proliferation, metastasis, metabolism, tumorigenesis, and apoptosis. Dysregulation of miRNA expression has been implicated in human cancers, and they may also serve as biomarkers of disease progression and prognosis. The miR-17-92 cluster is one of the most widely studied miRNA clusters, which was initially reported as an oncogene, but was later reported to exhibit tumour suppressive effects in some human cancers. This review summarizes the recent progress and context-dependant role of this cluster in various cancers. We summarize the known mechanisms which regulate miR-17-92 expression and molecular pathways that are in turn controlled by it. We discuss examples where it acts as an oncogene or a tumour suppressor along with key targets affecting hallmarks of cancer. We discuss how cellular contexts regulate the biological effects of miR-17-92. The plausible mechanisms of its paradoxical roles are explained, and mechanisms are described that may contribute to cell fate regulation by miR-17-92. Further, we discuss recently developed strategies to target miR-17-92 cluster in human cancers. MiR-17-92 may serve as a potential biomarker for prognosis and response to therapy as well as a target for cancer prevention and therapeutics.

Lung cancer is the primary cause of cancer related deaths worldwide. Limited therapeutic options and resistance to existing drugs are the major hindrances to the clinical success of this cancer. In the past decade, several studies showed the role of microRNA (miRNA) driven cell cycle regulation in lung cancer progression. Therefore, these small nucleotide molecules could be utilized as promising tools in lung cancer therapy. In this review, we highlighted the recent advancements in lung cancer therapy using cell cycle linked miRNAs. By highlighting the roles of the specific cell cycle core regulators affiliated miRNAs in lung cancer, we further outlined how these miRNAs can be explored in early diagnosis and treatment strategies to prevent lung cancer. With the provided information from our review, more medical efforts can ensure a potential breakthrough in miRNA-based lung cancer therapy.