ncRNA Expression Research Articles

Epigenetic reprogramming in cancer: From diagnosis to treatment.

Disruption of the epigenetic program of gene expression is a hallmark of cancer that initiates and propagates tumorigenesis. Altered DNA methylation, histone modifications and ncRNAs expression are a feature of cancer cells. The dynamic epigenetic changes during oncogenic transformation are related to tumor heterogeneity, unlimited self-renewal and multi-lineage differentiation. This stem cell-like state or the aberrant reprogramming of cancer stem cells is the major challenge in treatment and drug resistance. Given the reversible nature of epigenetic modifications, the ability to restore the cancer epigenome through the inhibition of the epigenetic modifiers is a promising therapy for cancer treatment, either as a monotherapy or in combination with other anticancer therapies, including immunotherapies. Herein, we highlighted the main epigenetic alterations, their potential as a biomarker for early diagnosis and the epigenetic therapies approved for cancer treatment.

The Epigenetic Effects of Coffee.

In this review, we discuss the recent knowledge regarding the epigenetic effects of coffee extract and the three essential active ingredients in coffee (caffeine, chlorogenic acid, and caffeic acid). As a popular beverage, coffee has many active ingredients which have a variety of biological functions such as insulin sensitization, improvement of sugar metabolism, antidiabetic properties, and liver protection. However, recent researches have shown that coffee is not only beneficial for human, but also bad, which may be due to its complex components. Studies suggest that coffee extract and its components can potentially impact gene expression via alteration of DNA methylation, histone modifications, and ncRNA expression; thus, exert long lasting impacts on the epigenome. More importantly, coffee consumption during pregnancy has been linked to multiple negative effects on offspring due to epigenetic modifications; on the other hand, it has also been linked to improvements in many diseases, including cancer. Therefore, understanding more about the epigenetic effects associated with coffee components is crucial to finding ways for improving human health.

Prognostic and diagnostic values of non-coding RNAs as biomarkers for breast cancer: An umbrella review and pan-cancer analysis.

Background: Breast cancer (BC) is the most common cancer in women. The incidence and morbidity of BC are expected to rise rapidly. The stage at which BC is diagnosed has a significant impact on clinical outcomes. When detected early, an overall 5-year survival rate of up to 90% is possible. Although numerous studies have been conducted to assess the prognostic and diagnostic values of non-coding RNAs (ncRNAs) in breast cancer, their overall potential remains unclear. In this field of study, there are various systematic reviews and meta-analysis studies that report volumes of data. In this study, we tried to collect all these systematic reviews and meta-analysis studies in order to re-analyze their data without any restriction to breast cancer or non-coding RNA type, to make it as comprehensive as possible. Methods: Three databases, namely, PubMed, Scopus, and Web of Science (WoS), were searched to find any relevant meta-analysis studies. After thoroughly searching, the screening of titles, abstracts, and full-text and the quality of all included studies were assessed using the AMSTAR tool. All the required data including hazard ratios (HRs), sensitivity (SENS), and specificity (SPEC) were extracted for further analysis, and all analyses were carried out using Stata. Results: In the prognostic part, our initial search of three databases produced 10,548 articles, of which 58 studies were included in the current study. We assessed the correlation of non-coding RNA (ncRNA) expression with different survival outcomes in breast cancer patients: overall survival (OS) (HR = 1.521), disease-free survival (DFS) (HR = 1.33), recurrence-free survival (RFS) (HR = 1.66), progression-free survival (PFS) (HR = 1.71), metastasis-free survival (MFS) (HR = 0.90), and disease-specific survival (DSS) (HR = 0.37). After eliminating low-quality studies, the results did not change significantly. In the diagnostic part, 22 articles and 30 datasets were retrieved from 8,453 articles. The quality of all studies was determined. The bivariate and random-effects models were used to assess the diagnostic value of ncRNAs. The overall area under the curve (AUC) of ncRNAs in differentiated patients is 0.88 (SENS: 80% and SPEC: 82%). There was no difference in the potential of single and combined ncRNAs in differentiated BC patients. However, the overall potential of microRNAs (miRNAs) is higher than that of long non-coding RNAs (lncRNAs). No evidence of publication bias was found in the current study. Nine miRNAs, four lncRNAs, and five gene targets showed significant OS and RFS between normal and cancer patients based on pan-cancer data analysis, demonstrating their potential prognostic value. Conclusion: The present umbrella review showed that ncRNAs, including lncRNAs and miRNAs, can be used as prognostic and diagnostic biomarkers for breast cancer patients, regardless of the sample sources, ethnicity of patients, and subtype of breast cancer.

A Cocktail of Polyherbal Bioactive Compounds and Regular Mobility Training as Senolytic Approaches in Age-dependent Alzheimer's: the In Silico Analysis, Lifestyle Intervention in Old Age.

Alzheimer's is a principal concern globally. Machine learning is a valuable tool to determine protective and diagnostic approaches for the elderly. We analyzed microarray datasets of Alzheimer's cases based on artificial intelligence by R statistical software. This study provided a screened pool of ncRNAs and coding RNAs related to Alzheimer's development. We designed hub genes as cut points in networks and predicted potential microRNAs and LncRNA to regulate protein networks in aging and Alzheimer's through in silico algorithms. Notably, we collected effective traditional herbal medicines. A list of bioactive compounds prepared including capsaicin, piperine, crocetin, safranal, saffron oil, coumarin, thujone, rosmarinic acid, sabinene, thymoquinone, ascorbic acid, vitamin E, cyanidin, rhaponticin, isovitexin, coumarin, nobiletin, evodiamine, gingerol, curcumin, quercetin, fisetin, and allicin as an effective fusion that potentially modulates hub proteins and molecular signaling pathways based on pharmacophore model screening and chemoinformatics survey. We identified profiles of 21 mRNAs, 272 microRNAs, and eight LncRNA in Alzheimer's based on prediction algorithms. We suggested a fusion of senolytic herbal ligands as an alternative therapy and preventive formulation in dementia. Also, we provided ncRNAs expression status as novel monitoring strategies in Alzheimer's and new cut-point proteins as novel therapeutic approaches. Synchronizing fusion drugs and lifestyle could reverse Alzheimer's hallmarks to amelioration via an offset of the signaling pathways, leading to increased life quality in the elderly.

Human Breast Milk Omics and Neurodevelopment.

Breast milk is the ideal food for the premature and mature babies and has undoubtedly immediate and ultimate benefits. Among other things, it protects against infections, reduces the risk of necrotizing enterocolitis and retinopathy of the premature babies, improves neurodevelopmental outcome, and reduces the risk of obesity and metabolic syndrome later in life. In the present study, breast milk will be studied with all the available omics technologies. More specifically, functional genomics, comparative genomics, transcriptomics, sequencing, proteomics, and metabolomics will be performed. The above results and this multidimensional information will be coordinated under the framework of a holistic approach of systems biology and bioinformatic analysis. Important IncRNAs and protein molecules will be validated as candidate biomarkers in exosomes of a larger group of breast milk and blood/serum samples. Validated ncRNAs/proteins will be analyzed in exudates of breast milk and bovine, goat, and sheep milk to explore new ways to improve milk synthesis. Expression of ncRNAs, unlike mRNAs, is a direct indicator of their functional presence. The information to be generated in this study will be analyzed by mining and data combining techniques and algorithms. After defining breast milk molecular fingerprinting, an attempt will be made to enhance the commercial product. The benefits of breast milk are attributed to its various components, including nutrients, hormones, growth factors, immune cells, antibodies, cytokines, antimicrobial peptides, and extracellular vesicles.

Functional roles, regulatory mechanisms and theranostics applications of ncRNAs in alcohol use disorder.

Alcohol use disorder (AUD) is one of the most prevalent neuropsychological disorders worldwide, and its pathogenesis is convoluted and poorly understood. There is considerable evidence demonstrating significant associations between multiple heritable factors and the onset and progression of AUD. In recent years, a substantial body of research conducted by emerging biotechnologies has increasingly highlighted the crucial roles of noncoding RNAs (ncRNAs) in the pathophysiology of mental diseases. As in-depth understanding of ncRNAs and their mechanisms of action, they have emerged as prospective diagnostic indicators and preclinical therapeutic targets for a variety of psychiatric illness, including AUD. Of note, dysregulated expression of ncRNAs such as circRNAs, lncRNAs and miRNAs was routinely found in AUD individuals, and besides, exogenous regulation of partial ncRNAs has also been shown to be effective in ameliorating alcohol preference and excessive alcohol consumption. However, the exact molecular mechanism still remains elusive. Herein, we systematically summarized current knowledge regarding alterations in the expression of certain ncRNAs as well as their-mediated regulatory mechanisms in individuals with AUD. And finally, we detailedly reviewed the potential theranostics applications of gene therapy agents targeting ncRNAs in AUD mice. Overall, a deeper comprehension of functional roles and biological mechanisms of ncRNAs may make significant contributions to the accurate diagnosis and effective treatment of AUD.

The interplay between non-coding RNAs and alternative splicing: from regulatory mechanism to therapeutic implications in cancer.

Alternative splicing (AS) is a common and conserved process in eukaryotic gene regulation. It occurs in approximately 95% of multi-exon genes, greatly enriching the complexity and diversity of mRNAs and proteins. Recent studies have found that in addition to coding RNAs, non-coding RNAs (ncRNAs) are also inextricably linked with AS. Multiple different types of ncRNAs are generated by AS of precursor long non-coding (pre-lncRNAs) or precursor messenger RNAs (pre-mRNAs). Furthermore, ncRNAs, as a novel class of regulators, can participate in AS regulation by interacting with the cis-acting elements or trans-acting factors. Several studies have implicated abnormal expression of ncRNAs and ncRNA-related AS events in the initiation, progression, and therapy resistance in various types of cancers. Therefore, owing to their roles in mediating drug resistance, ncRNAs, AS-related factors and AS-related novel antigens may serve as promising therapeutic targets in cancer treatment. In this review, we summarize the interaction between ncRNAs and AS processes, emphasizing their great influences on cancer, especially on chemoresistance, and highlighting their potential values in clinical treatment.

Non-Coding RNA: An Emerging Modulator of ꞵ-Globin Regulation and ꞵ-Hemoglobinopathies

ꞵ-Hemoglobinopathies, including ꞵ-thalassemia and sickle cell anemia, are the most common autosomal receiver disorders, globally. Non-coding RNAs (ncRNAs) are derived from exons or introns of protein-coding genes or intronic regions of non-coding genes. There is significant evidence that these ncRNAs may act as protein decoys to impact a variety of biological functions, signaling, transcriptional regulators, cell differentiation, morphogenesis, and developmental regulation. The aberrant regulation of ncRNA expression serves as a hallmark of many hematological disorders, and there is solid evidence that these RNA species can play key roles in the pathogenesis of ꞵ-hemoglobinopathies. In the present review, we provide a summary of recent research findings about the role of ncRNA in globin gene regulation and ꞵ-hemoglobinopathies and their potential as therapeutic targets or prognostic and diagnostic biomarkers.

Non-Coding RNAs in Airway Diseases: A Brief Overview of Recent Data

Inflammation of the human lung is mediated in response to different stimuli (e.g., physical, radioactive, infective, pro-allergenic, or toxic) such as cigarette smoke and environmental pollutants. These stimuli often promote an increase in different inflammatory activities in the airways, manifesting themselves as chronic diseases (e.g., allergic airway diseases, asthma chronic bronchitis/chronic obstructive pulmonary disease, or even lung cancer). Non-coding RNA (ncRNAs) are single-stranded RNA molecules of few nucleotides that regulate the gene expression involved in many cellular processes. ncRNA are molecules typically involved in the reduction of translation and stability of the genes of mRNAs s. They regulate many biological aspects such as cellular growth, proliferation, differentiation, regulation of cell cycle, aging, apoptosis, metabolism, and neuronal patterning, and influence a wide range of biologic processes essential for the maintenance of cellular homeostasis. The relevance of ncRNAs in the pathogenetic mechanisms of respiratory diseases has been widely established and in the last decade many papers were published. However, once their importance is established in pathogenetic mechanisms, it becomes important to further deepen the research in this direction. In this review we describe several of most recent knowledge concerning ncRNA (overall miRNAs) expression and activities in the lung.

MicroRNAs and long non-coding RNAs in cartilage homeostasis and osteoarthritis.

During the last decade, osteoarthritis (OA) has become one of the most prevalent musculoskeletal diseases worldwide. OA is characterized by progressive loss of articular cartilage, abnormal remodeling of subchondral bone, hyperplasia of synovial cells, and growth of osteophytes, which lead to chronic pain and disability. The pathological mechanisms underlying OA initiation and progression are still poorly understood. Non-coding RNAs (ncRNAs) constitute a large portion of the transcriptome that do not encode proteins but function in numerous biological processes. Cumulating evidence has revealed a strong association between the changes in expression levels of ncRNA and the disease progression of OA. Moreover, loss- and gain-of-function studies utilizing transgenic animal models have demonstrated that ncRNAs exert vital functions in regulating cartilage homeostasis, degeneration, and regeneration, and changes in ncRNA expression can promote or decelerate the progression of OA through distinct molecular mechanisms. Recent studies highlighted the potential of ncRNAs to serve as diagnostic biomarkers, prognostic indicators, and therapeutic targets for OA. MiRNAs and lncRNAs are two major classes of ncRNAs that have been the most widely studied in cartilage tissues. In this review, we focused on miRNAs and lncRNAs and provided a comprehensive understanding of their functional roles as well as molecular mechanisms in cartilage homeostasis and OA pathogenesis.

Contribution of Non-Coding RNAs to Anticancer Effects of Dietary Polyphenols: Chlorogenic Acid, Curcumin, Epigallocatechin-3-Gallate, Genistein, Quercetin and Resveratrol.

Growing evidence has been accumulated to show the anticancer effects of daily consumption of polyphenols. These dietary polyphenols include chlorogenic acid, curcumin, epigallocatechin-3-O-gallate, genistein, quercetin, and resveratrol. These polyphenols have similar chemical and biological properties in that they can act as antioxidants and exert the anticancer effects via cell signaling pathways involving their reactive oxygen species (ROS)-scavenging activity. These polyphenols may also act as pro-oxidants under certain conditions, especially at high concentrations. Epigenetic modifications, including dysregulation of noncoding RNAs (ncRNAs) such as microRNAs, long noncoding RNAs, and circular RNAs are now known to be involved in the anticancer effects of polyphenols. These polyphenols can modulate the expression/activity of the component molecules in ROS-scavenger-triggered anticancer pathways (RSTAPs) by increasing the expression of tumor-suppressive ncRNAs and decreasing the expression of oncogenic ncRNAs in general. Multiple ncRNAs are similarly modulated by multiple polyphenols. Many of the targets of ncRNAs affected by these polyphenols are components of RSTAPs. Therefore, ncRNA modulation may enhance the anticancer effects of polyphenols via RSTAPs in an additive or synergistic manner, although other mechanisms may be operating as well.

Prediction of the cell-type-specific transcription of non-coding RNAs from genome sequences via machine learning.

Gene transcription is regulated through complex mechanisms involving non-coding RNAs (ncRNAs). As the transcription of ncRNAs, especially of enhancer RNAs, is often low and cell type specific, how the levels of RNA transcription depend on genotype remains largely unexplored. Here we report the development and utility of a machine-learning model (MENTR) that reliably links genome sequence and ncRNA expression at the cell type level. Effects on ncRNA transcription predicted by the model were concordant with estimates from published studies in a cell-type-dependent manner, regardless of allele frequency and genetic linkage. Among 41,223 variants from genome-wide association studies, the model identified 7,775 enhancer RNAs and 3,548 long ncRNAs causally associated with complex traits across 348 major human primary cells and tissues, such as rare variants plausibly altering the transcription of enhancer RNAs to influence the risks of Crohn's disease and asthma. The model may aid the discovery of causal variants and the generation of testable hypotheses for biological mechanisms driving complex traits.

Non-coding RNAs: The link between maternal malnutrition and offspring metabolism.

Early life nutrition is associated with the development and metabolism in later life, which is known as the Developmental Origin of Health and Diseases (DOHaD). Epigenetics have been proposed as an important explanation for this link between early life malnutrition and long-term diseases. Non-coding RNAs (ncRNAs) may play a role in this epigenetic programming. The expression of ncRNAs (such as long non-coding RNA H19, microRNA-122, and circular RNA-SETD2) was significantly altered in specific tissues of offspring exposed to maternal malnutrition. Changes in these downstream targets of ncRNAs lead to abnormal development and metabolism. This review aims to summarize the existing knowledge on ncRNAs linking the maternal nutrition condition and offspring metabolic diseases, such as obesity, type 2 diabetes (T2D) and non-alcoholic fatty liver disease (NAFLD).

Small non-coding RNA sequencing reveals global dysregulation of piwi-interacting RNA (piRNA) expression in gonadal malignant germ cell tumours.

Analyses of small non-coding RNA (ncRNA) expression in malignant germ cell tumours (GCTs) have focused on microRNAs (miRNAs). As GCTs all arise from primordial germ cells, and piwi-interacting RNAs (piRNAs) have important roles in maintaining germline integrity via transposon silencing, we hypothesised that malignant GCTs are characterised by fundamental piRNA dysregulation. We undertook global small ncRNA sequencing in malignant GCTs, in order to describe small ncRNA expression changes for both miRNAs and piRNAs. We performed small ncRNA next generation sequencing on a representative panel of 47 samples, comprising malignant GCT (n=31) and control (n=16) tissues/cell lines. Following quality control and normalisation, filtered count reads were used for differential miRNA and piRNA expression analyses via DESeq2. Predicted mRNA targets for piRNAs were identified and utilised for pathway enrichment analyses. Overall, miRNAs and piRNAs comprised 21.9% and 43.0% of small ncRNA species, respectively. There were 749 differentially expressed miRNAs in malignant GCTs, of which 536 (72%) were over-expressed and 213 (28%) under-expressed. The top-ranking over-expressed miRNAs were exclusively from the miR-371∼373 and miR-302/367 clusters. The most significantly under-expressed miRNAs were miR-100-5p, miR-214-3p, miR-125b-5p and let-7 family members, including miR-202-3p. There were 1,121 differentially expressed piRNAs in malignant GCTs, of which 167 (15%) were over-expressed and 954 (85%) under-expressed. Of note, of the top-20 differentially expressed piRNAs, 16 were over-expressed, of which piR-hsa-2506793 was both top-ranking and most abundant. Mobile element (ME; i.e., transposon)-associated piRNAs comprised 166 (15%) of the 1,121 differentially expressed piRNAs, of which 165 (>99%) were down-regulated. The remaining 955 (85%) non-ME-associated piRNAs may have wider cellular roles. To explore this, predicted mRNA targets of differentially expressed piRNAs identified putative involvement in cancer-associated pathways. This study confirms previous miRNA observations, giving credence to our novel demonstration of global piRNA dysregulation in gonadal malignant GCTs, through both ME and non-ME-associated pathways, which likely contributes to GCT pathogenesis.

Scatter Irradiation of Rat Brain Triggers Sex- and Brain Region-Specific Changes in the Expression of Non-Coding RNA Fragments.

Non-coding RNA fragments (ncRFs) are small RNA fragments processed from non-coding RNAs (ncRNAs). ncRFs have various functions and are commonly tissue-specific, and their processing is altered by exposure to stress. Information about ncRFs in the brain is scarce. Recently, we reported the brain region-specific and sex-specific expression of ncRNAs and their processing into ncRFs. Here, we analyzed the expression of ncRFs in the frontal cortex (FC), hippocampus (HIP), and cerebellum (CER) of male and female rats exposed to scatter radiation. We found multiple brain region- and sex-specific changes in response to scatter radiation. Specifically, we observed decreased miRNA expression and the increased expression of ra-ncRNA reads in HIP and CER, as well as an increased number of mtR-NA-associated reads in HIP. We also observed the appearance of sense-intronic ncRNAs-in females, in HIP and FC, and in males, in CER. In this work, we also show that tRNA-GlyGCC and tRNA-GlyCCC are most frequently processed to tRFs, in CER in females, as compared to males. An analysis of the targeted pathways revealed that tRFs and snoRFs in scatter radiation samples mapped to genes in several pathways associated with various neuronal functions. While in HIP and CER these pathways were underrepresented, in FC, they were overrepresented. Such changes may play an important role in pathologies that develop in response to scatter radiation, the effect known as "radio-brain", and may in part explain the sex-specific differences observed in animals and humans exposed to radiation and scatter radiation.

The Therapeutic Roles of Cinnamaldehyde against Cardiovascular Diseases.

Evidence from epidemiological studies has demonstrated that the incidence and mortality of cardiovascular diseases (CVDs) increase year by year, which pose a great threat on social economy and human health worldwide. Due to limited therapeutic benefits and associated adverse effects of current medications, there is an urgent need to uncover novel agents with favorable safety and efficacy. Cinnamaldehyde (CA) is a bioactive phytochemical isolated from the stem bark of Chinese herbal medicine Cinnamon and has been suggested to possess curative roles against the development of CVDs. This integrated review intends to summarize the physicochemical and pharmacokinetic features of CA and discuss the recent advances in underlying mechanisms and potential targets responsible for anti-CVD properties of CA. The CA-related cardiovascular protective mechanisms could be attributed to the inhibition of inflammation and oxidative stress, improvement of lipid and glucose metabolism, regulation of cell proliferation and apoptosis, suppression of cardiac fibrosis, and platelet aggregation and promotion of vasodilation and angiogenesis. Furthermore, CA is likely to inhibit CVD progression via affecting other possible processes including autophagy and ER stress regulation, gut microbiota and immune homeostasis, ion metabolism, ncRNA expression, and TRPA1 activation. Collectively, experiments reported previously highlight the therapeutic effects of CA and clinical trials are advocated to offer scientific basis for the compound future applied in clinical practice for CVD prophylaxis and treatment.

Comprehensive ceRNA network for MACF1 regulates osteoblast proliferation

BackgroundPrevious studies have shown that microtubule actin crosslinking factor 1 (MACF1) can regulate osteoblast proliferation and differentiation through non-coding RNA (ncRNA) in bone-forming osteoblasts. However, the role of MACF1 in targeting the competing endogenous RNA (ceRNA) network to regulate osteoblast differentiation remains poorly understood. Here, we profiled messenger RNA (mRNA), microRNA (miRNA), and long ncRNA (lncRNA) expression in MACF1 knockdown MC3TC‑E1 pre‑osteoblast cells.ResultsIn total, 547 lncRNAs, 107 miRNAs, and 376 mRNAs were differentially expressed. Significantly altered lncRNAs, miRNAs, and mRNAs were primarily found on chromosome 2. A lncRNA-miRNA-mRNA network was constructed using a bioinformatics computational approach. The network indicated that mir-7063 and mir-7646 were the most potent ncRNA regulators and mef2c was the most potent target gene. Pathway enrichment analysis showed that the fluid shear stress and atherosclerosis, p53 signaling, and focal adhesion pathways were highly enriched and contributed to osteoblast proliferation. Importantly, the fluid shear stress and atherosclerosis pathway was co-regulated by lncRNAs and miRNAs. In this pathway, Dusp1 was regulated by AK079370, while Arhgef2 was regulated by mir-5101. Furthermore, Map3k5 was regulated by AK154638 and mir-466q simultaneously. AK003142 and mir-3082-5p as well as Ak141402 and mir-446 m-3p were identified as interacting pairs that regulate target genes.ConclusionThis study revealed the global expression profile of ceRNAs involved in the differentiation of MC3TC‑E1 osteoblasts induced by MACF1 deletion. These results indicate that loss of MACF1 activates a comprehensive ceRNA network to regulate osteoblast proliferation.

Impact of MiRNAs and LncRNAs on Multidrug Resistance of Gastric Cancer.

Multi-drug resistance (MDR) is characterized by the resistance of tumor cells to some antitumor drugs with different structures and mechanisms after the use of a single chemotherapy drug or even the first use of the drug. Notably, MDR has become the largest obstacle to the success of gastric cancer chemotherapies. Non-coding RNAs are defined as a class of RNAs that do not have the ability to code proteins. They are widely involved in important biological functions in life activities. Multiple lines of evidence demonstrated that ncRNAs are closely related to human cancers, including gastric cancer. However, the relationship between ncRNAs and MDR in gastric cancer has been reported, yet the mechanisms are not fully clarified. Therefore, in this review, we systematically summarized the detailed molecular mechanisms of lncRNAs (long noncoding RNAs) and miRNAs (microRNAs) associated with MDR in gastric cancer. Additionally, we speculate that the abnormal expression of ncRNAs is likely to be a novel potential therapeutic target reversing MDR for gastric cancer. Future therapeutics for gastric cancer will most likely be based on noncoding RNAs (ncRNAs) that regulate MDR-related genes.

Pathophysiology of Ischemic Stroke: Noncoding RNA Role in Oxidative Stress.

Stroke is a neurological disease that causes significant disability and death worldwide. Ischemic stroke accounts for 75% of all strokes. The pathophysiological processes underlying ischemic stroke include oxidative stress, the toxicity of excitatory amino acids, ion disorder, enhanced apoptosis, and inflammation. Noncoding RNAs (ncRNAs) may have a vital role in regulating the pathophysiological processes of ischemic stroke, as confirmed by the altered expression of ncRNAs in blood samples from acute ischemic stroke patients, animal models, and oxygen-glucose-deprived (OGD) cell models. Due to specific changes in expression, ncRNAs can potentially be biomarkers for the diagnosis, treatment, and prognosis of ischemic stroke. As an important brain cell component, glial cells mediate the occurrence and progression of oxidative stress after ischemic stroke, and ncRNAs are an irreplaceable part of this mechanism. This review highlights the impact of ncRNAs in the oxidative stress process of ischemic stroke. It focuses on specific ncRNAs that underlie the pathophysiology of ischemic stroke and have potential as diagnostic biomarkers and therapeutic targets.

Recent insights into the microRNA and long non-coding RNA-mediated regulation of stem cell populations.

Stem cells are undifferentiated cells that have multi-lineage differentiation. The transition from self-renewal to differentiation requires rapid and extensive gene expression alterations. Since different stem cells exhibit diverse non-coding RNAs (ncRNAs) expression profiles, the critical roles of ncRNAs in stem cell reprogramming, pluripotency maintenance, and differentiation have been widely investigated over the past few years. Hence, in this current review, the two main categories of ncRNAs, microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), are discussed. While the primary way by which miRNAs restrict mRNA transcription is through miRNA-mRNA interaction, lncRNAs have a wide range of effects on mRNA functioning, including interactions with miRNAs. Both of these ncRNAs participate in the post-transcriptional regulation of crucial biological mechanisms, such as cell cycle regulation, apoptosis, aging, and cell fate decisions. These findings shed light on a previously unknown aspect of gene regulation in stem cell fate determination and behavior. Overall, we summarized the key roles of miRNAs (including exosomal miRNAs) and lncRNAs in the regulation of stem cell populations, such as cardiac, hematopoietic, mesenchymal, neural, and spermatogonial, as well ncRNAs' influence on malignancy through modulating cancer stem cells, which might significantly contribute to clinical stem cell therapy and in regenerative medicine.