MicroRNAs (miRNAs) are short non‑coding RNAs, which perform a key role in cellular differentiation and development. Most human diseases, particularly cancer, are linked to miRNA functional dysregulation implicated in the expression of tumor‑suppressive or oncogenic targets. Cancer hallmarks such as continued proliferative signaling, dodging growth suppressors, invasion and metastasis, triggering angiogenesis, and avoiding cell death have all been demonstrated to be affected by dysregulated miRNAs. Thus, for the treatment of different cancer types, the detection and quantification of this type of RNA is significant. The classical and current methods of RNA detection, including northern blotting, reverse transcription‑quantitative PCR, rolling circle amplification and next‑generation sequencing, may be effective but differ in efficiency and accuracy. Furthermore, these approaches are expensive, and require special instrumentation and expertise. Thus, researchers are constantly looking for more innovative approaches for miRNA detection, which can be advantageous in all aspects. In this regard, an RNA manipulation tool known as the CRISPR and CRISPR‑associated sequence 13 (CRISPR/Cas13) system has been found to be more advantageous in miRNA detection. The Cas13‑based miRNA detection approach is cost effective and requires no special instrumentation or expertise. However, more research and validation are required to confirm the growing body of CRISPR/Cas13‑based research that has identified miRNAs as possible cancer biomarkers for diagnosis and prognosis, and as targets for treatment. In the present review, current updates regarding miRNA biogenesis, structural and functional aspects, and miRNA dysregulation during cancer are described. In addition, novel approaches using the CRISPR/Cas13 system as a next‑generation tool for miRNA detection are discussed. Furthermore, challenges and prospects of CRISPR/Cas13‑based miRNA detection approaches are described.

Non-coding RNAs (ncRNAs), as critical regulators of gene expression, play a pivotal role in the modulation of pyroptosis and exhibit a close association with a wide range of diseases. Pyroptosis is a form of programmed cell death mediated by inflammasomes, characterized by cell membrane perforation, release of inflammatory cytokines, and a robust immune response. Recent studies have revealed that ncRNAs influence the initiation and execution of pyroptosis by regulating the expression of pyroptosis-related genes or modulating associated signaling pathways. This review systematically summarizes the molecular mechanisms and applications of ncRNAs in diseases such as cancer, infectious diseases, neurological disorders, cardiovascular diseases, and metabolic disorders. It further explores the potential of ncRNAs as diagnostic biomarkers and therapeutic targets, elucidates the intricate interactions among ncRNAs, pyroptosis, and diseases, and provides novel strategies and directions for the precision treatment of related diseases.

Breast cancer is an aggressive disease of multiple subtypes with varying phenotypic, hormonal, and clinicopathological features, offering enhanced resistance to conventional therapeutic regimens. There is an unmet need for reliable molecular biomarkers capable of detecting the malignant transformation from the early stages of the disease to enhance diagnosis and treatment outcomes. A subset of small non-coding nucleic acid molecules, micro ribonucleic acids (microRNAs/miRNAs), have emerged as promising biomarkers due to their role in gene regulation and cancer pathogenesis. This review discusses, in detail, the different origins and hormone-like regulatory functionalities of miRNAs localized in tumor tissue and in the circulation, as well as their inherent stability and turnover that determines the utility of miRNAs as biomarkers for disease detection, monitoring, prognosis, and therapeutic targets.

Epithelial-mesenchymal transition (EMT) has been extensively studied for its roles in tumor metastasis, the generation and maintenance of cancer stem cells and treatment resistance. Epithelial mesenchymal plasticity allows cells to switch between various states within the epithelial-mesenchymal spectrum, resulting in a mixed epithelial/mesenchymal phenotypic profile. This plasticity underlies the acquisition of multiple malignant features during cancer progression and poses challenges for EMT in tumors. MicroRNAs (miRNAs) in the microenvironment affect numerous signaling processes through diverse mechanisms, influencing physiological activities. This paper reviews recent advances in EMT, the role of different hybrid states in tumor progression, and the important role of miRNAs in EMT. Furthermore, it explores the relationship between miRNA-based EMT therapies and their implications for clinical practice, discussing how ongoing developments may enhance therapeutic outcomes.

Retinoblastoma (RB) is a common and potentially lethal cancer that primarily affects young children worldwide, with survival rates significantly varying between high- and low-income countries. This review aims to identify essential diagnostic markers for early diagnosis by investigating the molecular pathways associated with RB. The prevalence of RB cases is notably concentrated in Asia and Africa, contributing to a global survival rate estimate of less than 30%. Current management strategies involve complex, individualized treatment plans that consider cultural nuances, genetic abnormalities, staging, and the availability of medical resources. Recent studies suggest that circular RNAs (circRNAs) may serve as predictive and diagnostic biomarkers in the etiology of RB. This review examines the roles of long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and circRNAs in RB, with the goal of improving survival rates, particularly in low- and middle-income countries. A deeper understanding of the molecular pathways of RB may facilitate the development of personalized treatment plans and targeted therapies. Elevated expression of circRNAs has been observed in most patient cases, and studies indicate that reducing specific circRNA production can inhibit tumor cell development and progression. Investigating the roles and mechanisms of circular RNAs in RB holds promise for future treatment approaches.

Introduction Delayed cerebral ischemia (DCI) is a potentially preventable complication from an aneurysmal subarachnoid hemorrhage (SAH). The micro-RNAs (miR) 34 family has shown its ability to disrupt the blood-brain barrier and redox metabolism and might contribute to the complex pathophysiology of DCI. This study aimsto evaluate the association between the serum levels of miR-34c and the occurrence of DCI. Methods This retrospective observational study is based on 72 subjects with acute aneurysmal SAH who were admitted to a single tertiary center between December 2017 and July 2021. Subjects were prospectively adjudicated for clinical outcomes, including delayed cerebral ischemia.Levels of miR-34c were measured in plasma collected within 48 hours of ictus. Patients were median-dichotomized into having a higher or lower plasma level of miR-34c. miR34c levels were compared between DCI and no DCI groups using the Wilcoxon rank sum tests. A multivariable logistic regression model and the Cox proportional hazard model were used to evaluate the effect of higher miR-34c levels. Results The median age was 54 years, 76% were females, and 21% developed DCI. Early miR-34c levels were significantly higher in SAH subjects who progressed to have DCI with Cohen's d of 0.75 (p<0.05). Even after adjusting for age, sex, histories of diabetes, hypertension, Hunt-Hess grade, and modified Graeb scores, a higher miR-34c level was associated with 5.7-fold increased odds of DCI (p<0.05; 95% CI: 1.35-32.22). Survival analysis adjusting for the known predictors also revealeda 5.4-fold higher hazard of DCI for the patients with a higher miR-34c level (p < 0.05; 95% CI 1.22-25.43). Conclusion The present study demonstrates the potential importance of circulating miR-34c in predicting DCI in SAH patients. Given the known importance of the miR-34 family in vascular physiology, it may be an important target for future studies.

Colorectal cancer (CRC) ranks among the most prevalent cancers worldwide and is the fourth leading cause of cancer-related deaths. Metastasis poses a significant obstacle in CRC treatment, as distant metastasis, particularly to the liver, remains the primary cause of mortality. Colorectal liver metastasis (CRLM) occurs frequently due to the liver's direct vascular connection to the colorectal region via the portal vein. Standard treatment approaches for CRLM are limited; only a few patients qualify for surgical intervention, resulting in a persistently low survival rate. Additionally, resistance to chemotherapy is common, emphasizing the need for more effective targeted therapies. Emerging evidence highlights the pivotal role of microRNAs (miRNAs) in modulating critical pathways associated with CRLM, including tumor invasion, epithelial-mesenchymal transition, and angiogenesis. MiRNAs exhibit dual functions as tumor suppressors and oncogenes by targeting multiple genes, thus playing a complex role in both the initiation and progression of metastasis. The regulatory mechanisms of miRNAs could help to identify novel biomarkers for early diagnosis and prognosis of CRLM, as well as promising therapeutic targets to overcome chemoresistance. Despite numerous studies on miRNA involvement in CRC metastasis, dedicated reviews focusing on miRNAs and CRLM remain scarce. This review aims to approach targeted therapies by examining the current understanding of miRNA involvement in CRLM and exploring their potential as diagnostic, prognostic, and therapeutic agents. Through an integrative approach, we aim to provide insights that could transform CRLM management and improve patient outcomes.

This study investigates the impact of extracellular glucose concentrations on antioxidant capacity, viability, and microRNA (miR) expression in TM4 Sertoli cell lines. TM4 cells were cultured in high-glucose (115 µm) and low-glucose (<505 µm) conditions to simulate hyperglycemia and glucose starvation, respectively. The study measured total antioxidant capacity (TAC), malondialdehyde (MDA), total oxidant status (TOS), glutathione (GSH), glutathione disulfide (GSSG), NADP/NADPH, glutathione peroxidase (GPX), and glutathione reductase (GR) levels. MiR-17, miR-34, miR-106a, and miR-200a expression levels were assessed. Cell viability and apoptosis were evaluated using MTT assay and acridine-orange staining. Results indicated that high glucose reduced miR-17 expression while low glucose increased it. Both glucose conditions elevated miR-34, miR-106a, and miR-200a expressions. TAC levels decreased, while TOS and MDA levels increased significantly under both conditions. High glucose had no significant effect on GPX and GR levels, whereas low glucose decreased them. Both conditions led to reduced GSH levels, increased GSSG levels, and altered NADP/NADPH ratio. Increased apoptosis and decreased cell viability were observed under both glucose conditions. These findings suggest that extracellular glucose levels significantly dysregulate miRNA expression, antioxidant capacities, and redox buffer systems in TM4 cells. High glucose conditions suppress miR-17 expression, increase miR-34 and miR-106a levels, and induce reductive buffer imbalance. Conversely, low glucose conditions trigger compensatory mechanisms via increased miR-17 expression to enhance antioxidant status while reducing GPX and GR levels. These results provide insights into the molecular responses of Sertoli cells under varying glucose environments, highlighting potential therapeutic pathways for conditions like diabetes and metabolic dysfunctions.

Nucleic acid therapeutics have become increasingly recognized in recent years for their capability to target both coding and non-coding sequences. Several types of nucleic acid modalities, including siRNA, mRNA, aptamer, along with antisense oligo, have been approved by regulatory bodies for therapeutic use. The field of nucleic acid therapeutics has been brought to the forefront by the rapid development of vaccines against COVID-19, followed by a number of approvals for clinical use including much anticipated CRISPR-Cas9. However, obstacles such as the difficulty of achieving efficient and targeted delivery to diseased sites remain. This review provides an overview of nucleic acid therapeutics and highlights substantial advancements, including critical engineering, conjugation, and delivery strategies, that are paving the way for their growing role in modern medicine.

Sperm-borne microRNAs play a pivotal role in influencing essential cellular processes during fertilization, impacting the quality of embryo development. Dysregulated microRNA profiles have been associated with compromised embryonic development and increased incidences of pregnancy loss.

This study aimed to investigate the potential associations between the abundance of miR-34c-5p and miR-191-3p in human spermatozoa with sperm quality, as well as with embryo quality and metabolic performance during in vitro development.

Thirteen couples who underwent a total of 13 cycles participated in this study. The sperm quality was assessed using conventional methods following World Health Organization guidelines. Quantitative polymerase chain reaction was employed to measure microRNA abundance in spermatozoa. Embryos were categorized as good, lagging, or bad based on morphokinetic evaluation. Evaluation of embryo metabolic performance involved tracking changes in specific metabolites within the cultured media using nuclear magnetic resonance spectroscopy. Statistical analysis was conducted to explore the correlation between microRNA abundance in human spermatozoa and all other collected data.

Our findings revealed a negative correlation between the abundance of miR-34c-5p (but not miR-191-3p) and total sperm motility, potentially mediated by the modulation of key signaling pathways. Additionally, higher levels of miR-34c-5p in spermatozoa were strongly associated with the consumption or release of key metabolites by developing embryos, particularly those linked with lipid and glucose metabolism, suggesting enhanced metabolic performance, while miR-191-3p was mostly associated with glucose consumption. Concurrently, only miR-34c-5p content in spermatozoa correlated with higher embryo quality.

This study provides evidence suggesting that the abundance of miR-34c-5p in spermatozoa is correlated not only with total sperm motility but also with markers of embryo developmental competence, highlighting the potential significance of this sperm microRNA content as a biomarker in assisted reproduction.

Autophagy has been implicated in the pathogenesis and progression of spinal cord injury (SCI); however, its specific mechanisms remain unclear. This study is aimed at identifying potential molecular biomarkers related to autophagy in SCI through bioinformatics analysis and exploring potential therapeutic targets. The mRNA expression profile dataset GSE151371 was obtained from the GEO database, and R software was used to screen for differentially expressed autophagy-related genes (DE-ARGs) in SCI. A total of 39 DE-ARGs were detected in this study. Enrichment analysis, protein-protein interaction (PPI) network, TF-mRNA-miRNA regulatory network analysis, and the DSigDB database were used to investigate the regulatory mechanisms between DE-ARGs and identify potential drugs for SCI. Enrichment analysis revealed associations with autophagy, apoptosis, and cell death. PPI analysis identified the highest-scoring module and selected 10 hub genes to construct the TF-mRNA-miRNA network, revealing regulatory mechanisms. Analysis of the DSigDB database indicated that 1,9-Pyrazoloanthrone may be a potential therapeutic drug. Machine learning algorithms identified 3 key genes as candidate biomarkers. Additionally, immune cell infiltration results revealed significant correlations between PINK1, NLRC4, VAMP3, and immune cell accumulation. Molecular docking simulations revealed that imatinib can exert relatively strong regulatory effects on the three key proteins. Finally, in vivo experimental data revealed that the overall biological process of autophagy was disrupted. In summary, this study successfully identified 39 DE-ARGs and discovered several promising biomarkers, significantly contributing to our understanding of the underlying mechanisms of autophagy in SCI. These findings offer valuable insights for the development of novel therapeutic strategies.

Inappropriate aldosterone production relative to sodium status is known to induce arterial hypertension and cause detrimental effects on endothelium and vascular remodeling. This study investigated whether microRNAs (miRs) serve as key mediators of aldosterone's effects on endothelial dysfunction. Using human umbilical vein endothelial cells (HUVECs) as a model system, we demonstrated that aldosterone treatment suppressed cellular proliferation and migration while promoting senescence. Mechanistically, we observed that aldosterone exposure significantly upregulated miR-34a expression in HUVECs. The functional significance of miR-34a was confirmed when specific inhibitors reversed aldosterone's antiproliferative and prosenescence effects. To elucidate the underlying molecular pathway, we performed comprehensive biological analyses, which revealed that miR-34a target genes were predominantly associated with the Notch signaling pathway. Western blot analysis further validated that miR-34a promotes senescence in HUVECs through negative regulation of NOTCH1. Collectively, our findings identify miR-34a as a crucial mediator of aldosterone-induced endothelial cell senescence via the NOTCH1 signaling pathway, suggesting its potential as a therapeutic target for aldosterone-related vascular diseases.

Bladder cancer (BC) is a malignant tumor characterized by a high incidence of urinary system diseases. The complex pathogenesis of BC has long been a focal point in medical research. With the robust development of epigenetics, the crucial role of epigenetic modifications in the occurrence and progression of BC has been elucidated. These modifications not only affect gene expression but also impact critical biological behaviors of tumor cells, including proliferation, differentiation, apoptosis, invasion, and metastasis. Notably, DNA methylation, an important epigenetic regulatory mechanism, often manifests as global hypomethylation or hypermethylation of specific gene promoter regions in BC. Alterations in this methylation pattern can lead to increased genomic instability, which profoundly influences the expression of proto-oncogenes and tumor suppressor genes. MiRNAs, as noncoding small RNAs, participate in various biological processes of BC by regulating target genes. Consequently, this work aims to explore the interaction mechanisms between DNA methylation and miRNAs in the occurrence and development of BC. Research has demonstrated that DNA methylation not only directly influences the expression of miRNA genes but also indirectly affects the maturation and functionality of miRNAs by modulating the methylation status of miRNA promoter regions. Simultaneously, miRNAs can regulate DNA methylation levels by targeting key enzymes such as DNA methyltransferases (DNMTs), thereby establishing a complex feedback regulatory network. A deeper understanding of the crosstalk mechanisms between DNA methylation and miRNAs in BC will contribute to elucidating the complexity and dynamics of epigenetic modifications in this disease, and may provide new molecular targets and strategies for the early diagnosis, treatment, and prognostic evaluation of BC.

Breast cancer (BC) is a health concern worldwide and is often accompanied by depressive symptoms in patients. In BC, elevated interleukin-6 (IL-6) levels contribute to an inflammatory signature linked to cancer stem cell (CSC) stemness and depressive behaviors. Bioactive food components, such as berberine (BBR), have preventative effects against BC by targeting CSCs.

This study aimed to investigate the effects of BBR on breast CSC proliferation, on levels of specific micro (mi)RNAs and IL-6 in vitro and in vivo, and in alleviating depressive-like behaviors in mice with BC.

Mammosphere formation assays were conducted by treating murine 4T1 and human MDA-MB-231 BC cell lines with BBR. qPCR analysis of miRNAs miR-let-7c and miR-34a-5p was performed on 4T1 CSCs exposed to BBR. BBR was administered orally to female BALB/c, followed by injection with mammary carcinoma cells to induce BC. Behavioral tests were conducted to assess depressive-like behaviors. Tumor tissues were collected for ex vivo mammosphere assays, miRNA expression analysis, and IL-6 detection by ELISA. Serum was also collected for IL-6 analysis.

BBR treatment inhibited mammosphere formation and proliferation of CSCs derived from 4T1 and MDA-MB-231 cell lines. Quantification of mammosphere formation showed a significant decrease in both cell lines at 75 μM BBR (4T1: P < 0.001; MDA-MB-231: P < 0.0001). BBR upregulated the expression of miRNAs miR-let-7c and miR-34a in both cell lines, with miR-34a showing a significant increase (P < 0.001) and let-7c showing a significant increase (P < 0.05) in expression. In vivo, oral administration of BBR reduced mammosphere formation in breast tumor tissues (P < 0.0001) and elevated expression of miR-145 and miR-34a, with both showing significant upregulation (P < 0.0001), indicating its potential tumor-suppressive effects. BBR treatment resulted in a significant decrease in serum IL-6 levels (P < 0.05), suggesting anti-inflammatory properties, while the IL-6 in tumor tissue did not show significant changes (P > 0.05). However, no significant differences were observed in depressive-like behaviors between control and treatment groups.

BBR may have the potential to be used as an "Epi-Natural Compound" to prevent cancer by reducing inflammation and affecting epigenetics.

MiRNAs are short non-coding RNA molecules that have been shown to affect a vast number of genes at the post-transcriptional level, hence regulating several signaling pathways. Because the miRNA-34 family regulates a number of different signaling pathways, including those linked to cancer, the immune system, metabolism, cellular structure, and neurological disorders, it has garnered a great deal of attention from researchers. Members of the miRNA-34 family have been shown to inhibit tumors in a variety of cancer types. This family is also important for obesity, the cardiovascular system, and glycolysis. It's interesting to note that the miRNA-34 family is known to play a role in major depressive disorder, schizophrenia, Parkinson's disease (PD), adverse childhood experiences or trauma, regulation of stress responses, Alzheimer's disease (AD), and stress-related psychatric conditions. In this review, the expected targets of the miRNA-34 family are presented alongside the well-established targets identified by pathway analysis. Furthermore, the therapeutic potential of this miRNA family will be discussed.

Adverse effects of ionizing radiation on normal tissues limit the radiation dose in cancer treatment, thereby compromising treatment efficiency. Among the consistently affected non-cancer cells, peripheral blood mononuclear cells (PBMCs) exhibit high radiosensitivity and have the potential to induce systemic effects. PBMC-released extracellular vesicles (EVs), contribute to the communication of such systemic effects. This study aimed to investigate the effects of ionizing radiation on EVs as part of the systemic response of PBMCs in terms of microRNA cargo and biological functions.Therefore, whole blood samples from healthy donors were irradiated ex-vivo (0 Gy, 1 Gy, 2 Gy, 4 Gy) and EVs from PBMCs were isolated after 96 h by PEG precipitation or ultracentrifugation. Candidate microRNAs were examined in PBMC-derived EVs from individual donors. The uptake of membrane-stained fluorescent EVs by different recipient cells was quantified by fluorescence-activated cell sorting analysis. The biological effects of increased miR-34a-5p and of total EVs on recipient cells were assessed.Irradiation of PBMCs induced a dose-dependent upregulation of miR-34a-5p within EVs and PBMCs. However, interindividual differences between donors were noticed in the extent of upregulation, and small EVs displayed more pronounced changes in microRNA levels in comparison to large EVs. Irradiation in presence of the small molecule inhibitor KU-60019 demonstrated that this upregulation is dependent on ATM (Ataxia telangiectasia mutated) activation. Moreover, fibroblasts and keratinocytes were identified as preferred EV recipients. Increased miR-34a-5p levels led to a significant reduction in viability and induction of senescence in keratinocytes but not in fibroblasts, indicating a cell type-specific response.In conclusion, this study further elucidated the complex cellular response of normal tissue after radiation exposure. It confirmed radiation-induced modifications of microRNA expression levels in EVs from PBMCs and identified a robust upregulation of miR-34a-5p in the small EV subfraction, suggesting this microRNA as a potential novel candidate for the development of biomarkers for radiation exposure. Moreover, the different uptake efficiencies observed among specific cell types suggested that EVs induce cell type-specific responses in the intercellular communication of systemic radiation effects.

Prenatal exposure to air pollution is a significant risk factor for the mother and the developing foetus. The accumulation of pollutants in the placenta can cause a self-cascade loop of pro-inflammatory cytokine responses and DNA double-strand breaks. Previous research has shown that airborne particulate matter can damage the epigenome and disturb mitochondrial machinery, ultimately impairing placental function. Mitochondria are essential for preserving cellular homeostasis, energy metabolism, redox equilibrium, and epigenetic reprogramming. As these organelles are subtle targets of environmental exposures, any disruption in the signaling pathways can result in epigenomic instability, which can impact gene expression and mitochondrial function. This, in turn, can lead to changes in DNA methylation, post-translational histone modifications, and aberrant expression of microRNAs in proliferating trophoblast cells. The placenta has two distinct layers, cytotrophoblasts, and syncytiotrophoblasts, each with its mitochondria, which play important roles in preeclampsia, gestational diabetes, and overall health. Foetal nucleic acids enter maternal circulation during placental development because of necrotic, apoptotic, and inflammatory mechanisms. These nucleic acids reflect normal or abnormal ongoing cellular changes during prenatal foetal development. Detecting cell-free DNA in the bloodstream can be a biomarker for predicting negative pregnancy-related outcomes and recognizing abnormalities in foetal growth. Hence, a thorough understanding of how air pollution induces epigenetic variations within the placenta could offer crucial insights into underlying mechanisms and prolonged repercussions on foetal development and susceptibility in later stages of life.

Presbycusis, also referred to as age-related hearing loss (ARHL), is a multifaceted condition caused by the natural aging process affecting the auditory system. Genome-wide association studies (GWAS) in human populations can identify potential genes linked to ARHL. Despite this, our knowledge of the biochemical and molecular mechanisms behind the condition remains incomplete. This study aims to evaluate a potential protective tool for ARHL treatment by comparing human blood-based target gene-miRNA associations regulated in ARHL. To identify promising target genes for ARHL, we utilized an mRNA assay. To determine the role of miRNA in ARHL, we investigated the expression profile of miRNA in whole blood in ARHL patients with real-time polymerase chain reaction (RT-qPCR). A reporter gene assay was performed to confirm the regulation of candidate genes by microRNA. Through RT-qPCR validation analysis, we finally confirmed the relationship between ARHL and the role of the interferon-gamma (IFNG) gene. This gene can be regarded as an age-related gene. Through gene ontology (GO) analysis, it has been found that these genes are enriched in pathways related to apoptosis. Among them, IFNG induces an inflammatory response, apoptotic cell death, and cellular senescence. We found that miR-409-3p downregulates the expression of the IFNG in vitro. In addition, the downregulation of the IFNG by miRNA 409-3p promoted cell apoptosis and suppressed proliferation. In conclusion, our study produced gene signatures and associated microRNA regulation that could be a protective key for ARHL patients. IFNG genes and miR-409-3p should be investigated for their usefulness as a new biomarker for treatment modality.

Lung cancer is one of the most common malignant tumors in humans and the leading cause of cancer-related deaths worldwide. The microRNA-34 (miR-34) family is dysregulated in various human cancers and is an important family of tumor suppressor genes among microRNAs. The miR-34 family is downregulated in lung cancer. It inhibits cell proliferation, metastasis, and invasion, arrests the cell cycle, and induces apoptosis or senescence by negatively regulating many oncogenes. It is commonly used to detect and treat lung cancer. This study describes the regulatory role of the miR-34 family in lung cancer and the associated research advances in treatment.

MiRNAs are a class of non-coding RNAs acting as gene expression regulators by modulating the lifespan of messenger RNA. Commonly referred to as the most frequent leukemia in the Western world, chronic lymphocytic leukemia (CLL) is a lymphoproliferative malignancy characterized by clonal expansion of CD19, CD23, and CD5-positive mature B-cells. While this pathology is regarded as less aggressive and has a variety of treatment options, the cause of its clinical heterogeneity is not yet understood. Moreover, the prognostic markers and treatment recommendations based on predictive markers are limited. This review aims to investigate some miRNAs that are dysregulated and possibly involved in CLL pathogenesis as a starting point for the proposal of new prognostic and predictive markers and, as more agents targeting miRNA expression become available, their potential role as therapeutic targets.

As an element with metalloid properties, arsenic is pervasively present in the environment and is recognized as a potent carcinogen. Consequently, the issue of human arsenic exposure has become a significant concern within the global public health sector. Numerous studies have indicated that arsenic induces cellular senescence through various mechanisms, including triggering epigenetic alterations, inducing the senescence-associated secretory phenotype (SASP), promoting telomere shortening, and causing mitochondrial dysfunction. This article collates and summarizes the latest research advancements on the involvement of cellular senescence in arsenic toxicity and explores the mechanisms of arsenic-induced toxicity. This study aims to provide new perspectives and directions for future research on arsenic toxicity and the development of prevention and treatment strategies.

Long noncoding RNAs (lncRNAs) participate in regulating skeletal muscle development. However, little is known about their role in regulating chicken myogenesis. In this study, we identified a novel lncRNA, lncMPD2, through transcriptome sequencing of chicken myoblasts at different developmental stages. Functionally, gain- and loss-of-function experiments showed that lncMPD2 inhibited myoblast proliferation and differentiation. Mechanistically, lncMPD2 directly bound to miR-34a-5p, and miR-34a-5p promoted myoblasts proliferation and differentiation and inhibited the mRNA and protein expression of its target gene THBS1. THBS1 inhibited myoblast proliferation and differentiation in vitro and delayed muscle regeneration in vivo. Furthermore, rescue experiments showed that lncMPD2 counteracted the inhibitory effects of miR-34a-5p on THBS1 and myogenesis-related gene mRNA and protein expression. In conclusion, lncMPD2 regulates the miR-34a-5p/THBS1 axis to inhibit the proliferation and differentiation of myoblasts and skeletal muscle regeneration. This study provides more insight into the molecular regulatory network of skeletal muscle development, identifying novel potential biomarkers for improving chicken quality and increasing chicken yield. In addition, this study provides a potential goal for breeding strategies that minimize muscle damage in chickens.

Bronchopulmonary dysplasia (BPD) is a chronic lung disease in premature infants characterized by alveolar dysplasia, vascular simplification and dysmorphic vascular development. Supplemental oxygen and mechanical ventilation commonly used as life-saving measures in premature infants may cause BPD. microRNAs (miRNAs), a class of small, non-coding RNAs, regulate target gene expression mainly through post-transcriptional repression. miRNAs play important roles in modulating oxidative stress, proliferation, apoptosis, senescence, inflammatory responses, and angiogenesis. These cellular processes play pivotal roles in the pathogenesis of BPD. Accumulating evidence demonstrates that miRNAs are dysregulated in the lung of premature infants with BPD, and in animal models of this disease, suggesting contributing roles of dysregulated miRNAs in the development of BPD. Therefore, miRNAs are considered promising biomarker candidates and therapeutic agents for this disease. In this review, we discuss how dysregulated miRNAs and their modulation alter cellular processes involved in BPD. We then focus on therapeutic approaches targeting miRNAs for BPD. This review provides an overview of miRNAs as biomarkers, and highlights potential pathogenic roles, and therapeutic strategies for BPD using miRNAs.

Sirtuins are pivotal in orchestrating numerous cellular pathways, critically influencing cell metabolism, DNA repair, aging processes, and oxidative stress. In recent years, the involvement of sirtuins in tumor biology has garnered substantial attention, with a growing body of evidence underscoring their regulatory roles in various aberrant cellular processes within tumor environments. This article delves into the sirtuin family and its biological functions, shedding light on their dual roles-either as promoters or inhibitors-in various cancers including oral, breast, hepatocellular, lung, and gastric cancers. It further explores potential anti-tumor agents targeting sirtuins, unraveling the complex interplay between sirtuins, miRNAs, and chemotherapeutic drugs. The dual roles of sirtuins in cancer biology reflect the complexity of targeting these enzymes but also highlight the immense therapeutic potential. These advancements hold significant promise for enhancing clinical outcomes, marking a pivotal step forward in the ongoing battle against cancer.

Prostate cancer is one of the most common malignancies among men worldwide. Besides genetic alterations, epigenetic modulations including DNA methylation, histone modifications and miRNA mediated alteration of gene expression are the key driving forces for the prostate tumor development and cancer progression. Aberrant expression and/or the activity of the epigenetic modifiers/enzymes, results in aberrant expression of genes involved in DNA repair, cell cycle regulation, cell adhesion, apoptosis, autophagy, tumor suppression and hormone response and thereby disease progression. Altered epigenome is associated with prostate cancer recurrence, progression, aggressiveness and transition from androgen-dependent to androgen-independent phenotype. These epigenetic modifications are reversible and various compounds/drugs targeting the epigenetic enzymes have been developed that are effective in cancer treatment. This chapter focuses on the epigenetic alterations in prostate cancer initiation and progression, listing different epigenetic biomarkers for diagnosis and prognosis of the disease and their potential as therapeutic targets. This chapter also summarizes different epigenetic drugs approved for prostate cancer therapy and the drugs available for clinical trials.

Bladder cancer (BC) is a highly frequent neoplasm in correlation with significant rate of morbidity, mortality, and cost. The onset of BC is predominantly triggered by environmental and/or occupational exposures to carcinogens, such as tobacco. There are two distinct pathways by which BC can be developed, including non-muscle-invasive papillary tumors (NMIBC) and non-papillary (or solid) muscle-invasive tumors (MIBC). The Cancer Genome Atlas project has further recognized key genetic drivers of MIBC along with its subtypes with particular properties and therapeutic responses; nonetheless, NMIBC is the predominant BC presentation among the suffering individuals. Radical cystoprostatectomy, radiotherapy, and chemotherapy have been verified to be the common therapeutic interventions in metastatic tumors, among which chemotherapeutics are more conventionally utilized. Although multiple chemo drugs have been broadly administered for BC treatment, cisplatin is reportedly the most effective chemo drug against the corresponding malignancy. Notwithstanding, tumor recurrence is usually occurred following the consumption of cisplatin regimens, particularly due to the progression of chemo-resistant trait. In this framework, non-coding RNAs (ncRNAs), as abundant RNA transcripts arise from the human genome, are introduced to serve as crucial contributors to tumor expansion and cisplatin chemo-resistance in bladder neoplasm. In the current review, we first investigated the best-known ncRNAs, i.e. microRNAs (miRNAs), long ncRNAs (lncRNAs), and circular RNAs (circRNAs), correlated with cisplatin chemo-resistance in BC cells and tissues. We noticed that these ncRNAs could mediate the BC-related cisplatin-resistant phenotype through diverse cellular processes and signaling mechanisms, reviewed here. Eventually, diagnostic and prognostic potential of ncRNAs, as well as their therapeutic capabilities were highlighted in regard to BC management.

MicroRNAs (miRNAs) are small RNA molecules that regulate more than 30% of genes in humans. Recent studies have revealed that miRNAs play a crucial role in tumorigenesis. Large sets of miRNAs in human tumors are under-expressed compared to normal tissues. Furthermore, experiments have shown that interference with miRNA processing enhances tumorigenesis. Multiple studies have documented the causal role of miRNAs in cancer, and miRNA-based anticancer therapies are currently being developed. This review primarily focuses on two key points: (1) miRNAs and their role in human cancer and (2) the regulation of tumor suppressors by miRNAs. The review discusses (a) the regulation of the tumor suppressor p53 by miRNA, (b) the critical role of the miR-144/451 cluster in regulating the Itch-p63-Ago2 pathway, and (c) the regulation of PTEN by miRNAs. Future research and the perspectives of miRNA in cancer are also discussed. Understanding these pathways will open avenues for therapeutic interventions targeting miRNA regulation.

The exogenous delivery of miRNA to mimic and restore miRNA-34a activity in various cancer models holds significant promise in cancer treatment. Nevertheless, its effectiveness is often impeded by challenges, including a short half-life, propensity for off-target accumulation, susceptibility to inactivation by blood-based enzymes, concerns regarding patient safety, and the substantial cost associated with scaling up. As a means of overcoming these barriers, we propose the development of miRNA-loaded Tat-A86 nanoparticles by virtue of Tat-A86's ability to shield the loaded agent from external environmental factors, reducing degradation and inactivation, while enhancing circulation time and targeted accumulation.

Genetically engineered Tat-A86, featuring 16 copies of the interleukin-4 receptor (IL-4R)-binding peptide (AP1), Tat for tumor penetration, and an elastin-like polypeptide (ELP) for presenting target ligands and ensuring stability, served as the basis for this delivery system. Comparative groups, including Tat-E60 and A86, were employed to discern differences in binding and penetration. The designed ELP-based nanoparticle Tat-A86 effectively condensed miRNA, forming stable nanocomplexes under physiological conditions. The miRNA/Tat-A86 formulation bound specifically to tumor cells and facilitated stable miRNA delivery into them, effectively inhibiting tumor growth. The efficacy of miRNA/Tat-A86 was further evaluated using three-dimensional spheroids of lewis lung carcinoma (LLC) as in vitro model and LLC tumor-bearing mice as an in vivo model. It was found that miRNA/Tat-A86 facilitates effective cell killing by markedly improving miRNA penetration, leading to a substantial reduction in the size of LLC spheroids. Compared to other controls, Tat-A86 demonstrated superior efficacy in suppressing the growth of 3D cellular aggregates. Moreover, at equivalent doses, miRNA-34a delivered by Tat-A86 inhibited the growth of LLC cells in allograft mice.

Overall, these studies demonstrate that Tat-A86 nanoparticles can deliver miRNA systemically, overcoming the basic hurdles impeding miRNA delivery by facilitating both miRNA uptake and stability, ultimately leading to improved therapeutic effects.

It is commonly assumed that gastrointestinal cancer is the most common form of cancer across the globe and is the leading contributor to cancer-related death. The intricate mechanisms underlying the growth of GI cancers have been identified. It is worth mentioning that both non-coding RNAs (ncRNAs) and certain types of RNA, such as circular RNAs (circRNAs), long non-coding RNAs (lncRNAs), and microRNAs (miRNAs), can have considerable impact on the development of gastrointestinal (GI) cancers. As a tumour suppressor, in the group of short non-coding regulatory RNAs is miR-34a. miR-34a silences multiple proto-oncogenes at the post-transcriptional stage by targeting them, which inhibits all physiologically relevant cell proliferation pathways. However, it has been discovered that deregulation of miR-34a plays important roles in the growth of tumors and the development of cancer, including invasion, metastasis, and the tumor-associated epithelial-mesenchymal transition (EMT). Further understanding of miR-34a's molecular pathways in cancer is also necessary for the development of precise diagnoses and effective treatments. We outlined the most recent research on miR-34a functions in GI cancers in this review. Additionally, we emphasize the significance of exosomal miR-34 in gastrointestinal cancers.

Current nucleic acid delivery methods have not achieved efficient, non-toxic delivery of miRNAs with tumor-specific selectivity. In this study, a new delivery system based on light-inducible gold-silver-gold, core-shell-shell (CSS) nanoparticles is presented. This system delivers small nucleic acid therapeutics with precise spatiotemporal control, demonstrating the potential for achieving tumor-specific selectivity and efficient delivery of miRNA mimics. The light-inducible particles leverage the photothermal heating of metal nanoparticles due to the local surface plasmonic resonance for controlled chemical cleavage and release of the miRNA mimic payload. The CSS morphology and composition result in a plasmonic resonance within the near-infrared (NIR) region of the light spectrum. Through this method, exogenous miR-34a-5p mimics are effectively delivered to human squamous cell carcinoma TE10 cells, leading to apoptosis induction without adverse effects on untransformed keratinocytes in vitro. The CSS nanoparticle delivery system is tested in vivo in Foxn1nu athymic nude mice with bilateral human esophageal TE10 cancer cells xenografts. These experiments reveal that this CSS nanoparticle conjugates, when systemically administered, followed by 850 nm light emitting diode irradiation at the tumor site, 6 h post-injection, produce a significant and sustained reduction in tumor volume, exceeding 87% in less than 72 h.

MicroRNAs (miRNAs) represent a new class of biomarkers in the context of connective tissue disorders. The miRNA expression profiles in peripheral blood mononuclear cells (PBMCs) of patients with polymyositis (PM) and dermatomyositis (DM) have not been fully elucidated. The objective is to investigate miRNAs expression profile in PBMCs of patients with PM/DM.

Microarray technology was used to identify differentially expressed miRNAs in PBMCs obtained from 6 untreated PM/DM patients and 3 healthy controls (HCs). TaqMan-based stem-loop real-time PCR detection was used for validation in a cohort of 34 PM/DM patients and 20 HCs.

Microarray analysis revealed 38 differentially expressed miRNAs (24 up-regulated and 14 down-regulated) in PM/DM patients compared to HCs. Four miRNAs (miR-320a, miR-335-3p, miR-34a-5p and miR-454-3p) were chosen for real-time PCR validation. The expression of miR-34a-5p was significantly upregulated in PM/DM group (P < 0.05). In subgroup analysis, miR-34a-5p was significantly upregulated in interstitial lung disease (ILD) group and DM group (P < 0.001). The level of SIRT1, a validated target of miR-34a, was significantly lower in PBMCs of PM/DM patients compared with HCs.

MiR-34a-5p may potentially participate in the pathogenesis of PM/DM through SIRT1, and may serve as a potential new biomarker for PM/DM-ILD.

Gallbladder cancer incidence has been increasing globally, and it remains challenging to expect long prognosis with the current systemic chemotherapy. We identified a novel nucleic acid-mediated therapeutic target against gallbladder cancer by using innovative organoid-based gallbladder cancer models generated from KrasLSL-G12D/+; Trp53f/f mice. Using comprehensive microRNA expression analyses and a bioinformatics approach, we identified significant microRNA-34a-5p downregulation in both murine gallbladder cancer organoids and resected human gallbladder cancer specimens. In three different human gallbladder cancer cell lines, forced microRNA-34a-5p expression inhibited cell proliferation and induced cell-cycle arrest at the G1 phase by suppressing direct target (CDK6) expression. Furthermore, comprehensive RNA sequencing revealed the significant enrichment of gene sets related to the cell-cycle regulators after microRNA-34a-5p expression in gallbladder cancer cells. In a murine xenograft model, locally injected microRNA-34a-5p mimics significantly inhibited gallbladder cancer progression and downregulated CDK6 expression. These results provide a rationale for promising therapeutics against gallbladder cancer by microRNA-34a-5p injection, as well as a strategy to explore therapeutic targets against cancers using organoid-based models, especially for those lacking useful genetically engineered murine models, such as gallbladder cancer.

Glioblastoma multiform (GBM) is a commonly diagnosed brain neoplasm with a poor prognosis. Accumulating evidence has highlighted the significance of microRNA (miR) dysregulation in tumor development and progression. This study investigated the effect of hsa-miR-34a-5p and its combination with temozolomide on GBM, the related molecular mechanisms, and the signaling pathway using in-silico and in-vitro approaches. The in-silico tumor bulk and single-cell RNA sequencing analyses were done on TCGA-GTEx, CGGA, GSE13276, GSE90603, and GSE182109 datasets. After selecting the A172 cell line, hsa-miR-34a-5p mimics were transfected, and the cell viability, migration, cell cycle, clonogenicity, and apoptosis of studied groups were studied using MTT, scratch, flow cytometry, colony formation, and Annexin V/PI assays. The mRNA expression of CASP9, CASP3, CASP8, MMP2, CD44, CDK6, CDK4, CCND1, RAF1, MAP2K1, MET, SRC, and CD274 was studied using qRT-PCR method. hsa-miR-34a-5p downregulated RAF1 expression, as the signaling factor of the MAPK pathway. The combined treatment significantly downregulated the expression of MET, SRC, and MAP2K1, leading to the inhibition of the MET/MAPK pathway compared to temozolomide. Besides exerting anti-tumoral effects on the cell viability, migration, cell cycle, apoptosis, and clonogenicity of A172 cells, its combination with temozolomide enhanced temozolomide anti-tumoral effect. Compared to temozolomide, the combined treatment significantly decreased CDK4, CDK6, CCND1, and MMP2 expression. hsa-miR-34a-5p targets RAF1, as the signaling factor of the MAPK pathway, and potentiates the temozolomide anti-tumoral effect on A172 cells.

MicroRNAs (miRs) are a group of small, 17-25 nucleotide, non-coding RNA that regulate gene expression at the post-transcriptional level. To date, little is known about the molecular signatures of regulatory interactions between miRs and apoptosis and oxidative stress in viral diseases. Lagovirus europaeus is a virus that causes severe disease in rabbits (Oryctolagus cuniculus) called Rabbit Hemorrhagic Disease (RHD) and belongs to the Caliciviridae family, Lagovirus genus. Within Lagovirus europaeus associated with RHD, two genotypes (GI.1 and GI.2) have been distinguished, and the GI.1 genotype includes four variants (GI.1a, GI.1b, GI.1c, and GI.1d). The study aimed to assess the expression of miRs and their target genes involved in apoptosis and oxidative stress, as well as their potential impact on the pathways during Lagovirus europaeus-two genotypes (GI.1 and GI.2) infection of different virulences in four tissues (liver, lung, kidneys, and spleen). The expression of miRs and target genes related to apoptosis and oxidative stress was determined using quantitative real-time PCR (qPCR). In this study, we evaluated the expression of miR-21 (PTEN, PDCD4), miR-16b (Bcl-2, CXCL10), miR-34a (p53, SIRT1), and miRs-related to oxidative stress-miR-122 (Bach1) and miR-132 (Nfr-2). We also examined the biomarkers of both processes (Bax, Bax/Bcl-2 ratio, Caspase-3, PARP) and HO-I as biomarkers of oxidative stress. Our report is the first to present the regulatory effects of miRs on apoptosis and oxidative stress genes in rabbit infection with Lagovirus europaeus-two genotypes (GI.1 and GI.2) in four tissues (liver, lungs, kidneys, and spleen). The regulatory effect of miRs indicates that, on the one hand, miRs can intensify apoptosis (miR-16b, miR-34a) in the examined organs in response to a viral stimulus and, on the other hand, inhibit (miR-21), which in both cases may be a determinant of the pathogenesis of RHD and tissue damage. Biomarkers of the Bax and Bax/Bcl-2 ratio promote more intense apoptosis after infection with the Lagovirus europaeus GI.2 genotype. Our findings demonstrate that miR-122 and miR-132 regulate oxidative stress in the pathogenesis of RHD, which is associated with tissue damage. The HO-1 biomarker in the course of rabbit hemorrhagic disease indicates oxidative tissue damage. Our findings show that miR-21, miR-16b, and miR-34a regulate three apoptosis pathways. Meanwhile, miR-122 and miR-132 are involved in two oxidative stress pathways.

Cardiovascular disease (CVD) continues to impose a significant global health burden, necessitating the exploration of innovative treatment strategies. Ribonucleic acid (RNA)-based therapeutics have emerged as a promising avenue to address the complex molecular mechanisms underlying CVD pathogenesis. We present a comprehensive review of the current state of RNA therapeutics in the context of CVD, focusing on the diverse modalities that bring about transient or permanent modifications by targeting the different stages of the molecular biology central dogma. Considering the immense potential of RNA therapeutics, we have identified common gene targets that could serve as potential interventions for prevalent Mendelian CVD caused by single gene mutations, as well as acquired CVDs developed over time due to various factors. These gene targets offer opportunities to develop RNA-based treatments tailored to specific genetic and molecular pathways, presenting a novel and precise approach to address the complex pathogenesis of both types of cardiovascular conditions. Additionally, we discuss the challenges and opportunities associated with delivery strategies to achieve targeted delivery of RNA therapeutics to the cardiovascular system. This review highlights the immense potential of RNA-based interventions as a novel and precise approach to combat CVD, paving the way for future advancements in cardiovascular therapeutics.

Serum aspartate transaminase (sAST) level is used routinely in conjunction with other clinical assays to assess liver health and disease. Increasing evidence suggests that sAST is associated with all-cause mortality and has prognostic value in several cancers, including gastrointestinal and urothelial cancers. Here, we undertake a systems approach to unravel molecular connections between AST and cancer prognosis, metabolism, and immune signatures at the transcriptomic and proteomic levels.

We mined public gene expression data across multiple normal and cancerous tissues using the Genotype Tissue Expression (GTEX) resource and The Cancer Genome Atlas (TCGA) to assess the expression of genes encoding AST isoenzymes (GOT1 and GOT2) and their association with disease prognosis and immune infiltration signatures across multiple tumors. We examined the associations between AST and previously reported pan-cancer molecular subtypes characterized by distinct metabolic and immune signatures. We analyzed human protein-protein interaction networks for interactions between GOT1 and GOT2 with cancer-associated proteins. Using public databases and protein-protein interaction networks, we determined whether the subset of proteins that interact with AST (GOT1 and GOT2 interactomes) are enriched with proteins associated with specific diseases, miRNAs and transcription factors.

We show that AST transcript isoforms (GOT1 and GOT2) are expressed across a wide range of normal tissues. AST isoforms are upregulated in tumors of the breast, lung, uterus, and thymus relative to normal tissues but downregulated in tumors of the liver, colon, brain, kidney and skeletal sarcomas. At the proteomic level, we find that the expression of AST is associated with distinct pan-cancer molecular subtypes with an enrichment of specific metabolic and immune signatures. Based on human protein-protein interaction data, AST physically interacts with multiple proteins involved in tumor initiation, suppression, progression, and treatment. We find enrichments in the AST interactomes for proteins associated with liver and lung cancer and dermatologic diseases. At the regulatory level, the GOT1 interactome is enriched with the targets of cancer-associated miRNAs, specifically mir34a - a promising cancer therapeutic, while the GOT2 interactome is enriched with proteins that interact with cancer-associated transcription factors.

Our findings suggest that perturbations in the levels of AST within specific tissues reflect pathophysiological changes beyond tissue damage and have implications for cancer metabolism, immune infiltration, prognosis, and treatment personalization.

Neuroinflammation is considered a balanced inflammatory response important in the intrinsic repair process after injury or infection. Under chronic states of disease, injury, or infection, persistent neuroinflammation results in a heightened presence of cytokines, chemokines, and reactive oxygen species that result in tissue damage. In the CNS, the surrounding microglia normally contain macrophages and other innate immune cells that perform active immune surveillance. The resulting cytokines produced by these macrophages affect the growth, development, and responsiveness of the microglia present in both white and gray matter regions of the CNS. Controlling the levels of these cytokines ultimately improves neurocognitive function and results in the repair of lesions associated with neurologic disease. MicroRNAs (miRNAs) are master regulators of the genome and subsequently control the activity of inflammatory responses crucial in sustaining a robust and acute immunological response towards an acute infection while dampening pathways that result in heightened levels of cytokines and chemokines associated with chronic neuroinflammation. Numerous reports have directly implicated miRNAs in controlling the abundance and activity of interleukins, TGF-B, NF-kB, and toll-like receptor-signaling intrinsically linked with the development of neurological disorders such as Parkinson's, ALS, epilepsy, Alzheimer's, and neuromuscular degeneration. This review is focused on discussing the role miRNAs play in regulating or initiating these chronic neurological states, many of which maintain the level and/or activity of neuron-specific secondary messengers. Dysregulated miRNAs present in the microglia, astrocytes, oligodendrocytes, and epididymal cells, contribute to an overall glial-specific inflammatory niche that impacts the activity of neuronal conductivity, signaling action potentials, neurotransmitter robustness, neuron-neuron specific communication, and neuron-muscular connections. Understanding which miRNAs regulate microglial activation is a crucial step forward in developing non-coding RNA-based therapeutics to treat and potentially correct the behavioral and cognitive deficits typically found in patients suffering from chronic neuroinflammation.

Molecular techniques can complement conventional spermiogram analyses to provide new information on the fertilizing potential of spermatozoa and to identify early alterations due to environmental pollution.

Here, we present a multilevel molecular profiling by small RNA sequencing and sperm nuclear basic protein analysis of male germ cells from 33 healthy young subjects residing in low and high-polluted areas.

Although sperm motility and sperm concentration were comparable between samples from the two sites, those from the high-pollution area had a higher concentration of immature/immune cells, a lower protamine/histone ratio, a reduced ability of sperm nuclear basic proteins to protect DNA from oxidative damage, and an altered copper/zinc ratio in sperm. Sperm levels of 32 microRNAs involved in intraflagellar transport, oxidative stress response, and spermatogenesis were different between the two areas. In parallel, a decrease of Piwi-interacting RNA levels was observed in samples from the high-polluted area.

This comprehensive analysis provides new insights into pollution-driven epigenetic alterations in sperm not detectable by spermiogram.

MicroRNAs (miRNAs) have emerged as pivotal regulators of gene expression, playing essential roles in diverse cellular processes, including the development and progression of cancer. Among the numerous proteins influenced by miRNAs, the MARCKS/MARCKSL1 protein, a key regulator of cellular cytoskeletal dynamics and membrane-cytosol communication, has garnered significant attention due to its multifaceted involvement in various cancer-related processes, including cell migration, invasion, metastasis, and drug resistance. Motivated by the encouraging early clinical success of peptides targeting MARCKS in several pathological conditions, this review article delves into the intricate interplay between miRNAs and the MARCKS protein in cancer. Herein, we have highlighted the latest findings on specific miRNAs that modulate MARCKS/MARCKSL1 expression, providing a comprehensive overview of their roles in different cancer types. We have underscored the need for in-depth investigations into the therapeutic feasibility of targeting the miRNA-MARCKS axis in cancer, taking cues from the successes witnessed in related fields. Unlocking the full potential of miRNA-mediated MARCKS regulation could pave the way for innovative and effective therapeutic interventions against various cancer types.

MicroRNAs (miRNAs) negatively affect gene expression by binding to their specific mRNAs resulting in either mRNA destruction or translational repression. The aberrant expression of various miRNAs has been associated with a number of human cancer. Oncogenic or tumor-suppressor miRNAs regulate a variety of pathways involved in the development of breast cancer (BC), including cell proliferation, apoptosis, metastasis, cancer recurrence, and chemoresistance. Variations in miRNA-encoding genes and their target genes lead to dysregulated gene expression resulting in the development and progression of BC. The various therapeutic approaches to treat the disease include chemotherapy, radiation therapy, surgical removal, hormone therapy, chemotherapy, and targeted biological therapy. The purpose of the current review is to explore the genetic variations in tumor-suppressor miRNA-encoding genes and their target genes in association with the disease development and prognosis. The therapeutic interventions targeting the variants for better disease outcomes have also been discussed.

To estimate the roles of extracellular vesicles (EVs) in tears and to determine whether their profiles are associated with the type of ocular disease.

Cross-sectional study.

Tear EVs were extracted from 14 healthy participants and from 21 patients with retinal diseases (age-related macular degeneration [AMD] or diabetic macular edema [DME]). The surface marker expression of tear EVs was examined, and microRNAs (miRNAs) were extracted and profiled by use of real-time PCR array. The stability of the expression of the miRNAs was determined, and their functions were assessed by network analyses. Classification accuracy was evaluated by use of a random forest classifier and k-fold cross-validation.

The miRNAs that were highly expressed in tear EVs were miR-323-3p, miR-548a-3p, and miR-516a-5p. The most stably expressed miRNAs independent of diseases were miR-520h and miR-146b-3p. The primary networks of the highly stably expressed endogenous miRNAs were annotated as regulation of organismal injury and abnormalities. The highly expressed miRNAs for severe retinal disease were miR-151-5p for AMD and miR-422a for DME, suggesting potential roles of tear EVs in liquid biopsy. Nine miRNAs (miR-25, miR-30d, miR-125b, miR-132, miR-150, miR-184, miR-342-3p, miR-378, and miR-518b) were identified as distinguishing individuals with AMD from healthy individuals with a classification accuracy of 91.9%.

The finding that tear EVs contain characteristic miRNA species indicates that they may help in maintaining homeostasis and serve as a potential tool for disease diagnosis.