Neural tube defects (NTDs) represent a significant burden on global pediatric health, contributing to high rates of infant mortality and morbidity. Despite extensive research into their etiology, NTDs continue to pose challenges in diagnosis and treatment. MicroRNAs (miRNAs) have emerged as promising candidates for understanding the molecular mechanisms underlying NTDs and potentially offering avenues for improved diagnosis and therapeutic intervention. This review explores the multifaceted roles of miRNAs in the context of NTD pathogenesis. Studies have identified specific miRNA profiles associated with NTDs, providing insights into their potential as diagnostic biomarkers. Furthermore, dysregulation of certain miRNAs has been implicated in the pathophysiology of NTDs, highlighting their role as potential therapeutic targets. Additionally, animal models and deep sequencing approaches have expanded our understanding of the diverse miRNA expression patterns associated with NTDs. By unraveling the intricate molecular mechanisms underlying NTD pathogenesis, miRNAs offer promising avenues for early detection and intervention, ultimately improving outcomes for affected individuals.

The elasticities of RNAs are generally essential for their biological functions, and RNAs often become functional when interacting with their binding proteins. However, the effects of binding proteins on the elasticities of double-stranded (ds) RNAs, such as twist-stretch coupling, still remain little understood. Here, our extensive all-atom molecular dynamics simulations show that the twist-stretch coupling of dsRNAs can be reversed from positive to negative by their binding proteins. Our analyses revealed that such a reversing effect of binding proteins is attributed to the protein anchoring across the major groove of dsRNAs, which alters the dominating deformation pathway from a major-groove-mediated one to a helical-radius-mediated one through two base-pair parameters of slide and inclination. Meanwhile, the anchoring effect from binding proteins on dsRNAs is further ascribed to the strong electrostatic attractions between dsRNAs and the positively charged binding domain of the proteins.

Ribonucleic acid (RNA)-based therapies represent a promising class of drugs for the treatment of non-small cell lung cancer (NSCLC) due to their ability to modulate gene expression. Therapies leveraging small interfering RNA (siRNA), messenger RNA (mRNA), microRNA (miRNA), and antisense oligonucleotides (ASOs) offer various advantages over conventional treatments, including the ability to target specific genetic mutations and the potential for personalized medicine approaches. However, the clinical translation of these therapeutics for the treatment of NSCLC faces challenges in delivery due to their immunogenicity, negative charge, and large size, which can be mitigated with delivery platforms. In this review, we provide a description of the pathophysiology of NSCLC and an overview of RNA-based therapeutics, specifically highlighting their potential application in the treatment of NSCLC. We discuss relevant classes of RNA and their therapeutic potential for NSCLC. We then discuss challenges in delivery and non-viral delivery strategies such as lipid- and polymer-based nanoparticles that have been developed to address these issues in preclinical models. Furthermore, we provide a summary table of clinical trials that leverage RNA therapies for NSCLC [which includes their National Clinical Trial (NCT) numbers] to highlight the current progress in NSCLC. We also discuss how these NSCLC therapies can be integrated with existing treatment modalities to enhance their efficacy and improve patient outcomes. Overall, we aim to highlight non-viral strategies that tackle RNA delivery challenges while showcasing RNA's potential as a next-generation therapy for NSCLC treatment.

Spray-induced gene silencing (SIGS) has become a new technology for pest and disease control in plants. This study synthesized three double-strand RNAs (dsRNAs) targeting Fusarium graminearum (F. graminearum), the major pathogen causing Fusarium head blight (FHB). Co-incubation showed weak uptake of dsRNA by F. graminearum, and some dsRNAs influence spore germination and hyphae growth. In contrast, exogenous dsRNA quickly and efficiently penetrates wheat leaves. Treatment of wheat leaves and detached wheat heads with these dsRNAs has a negative effect on the pathogenicity of F. graminearum. Foliar spraying of dsCHS3b or dsMGV1 decreased the amount of artificially inoculated F. graminearum, the incidence rate, and disease severity in the field. Under natural conditions, spraying dsRNAs significantly decreased the FHB disease index and deoxynivalenol content. Twice spray achieved more than 90% control of FHB. In conclusion, SIGS effectively prevents the infection of F. graminearum in wheat, providing a green way for FHB control.

Anthropogenic activities result in global change, including climate change, landscape degradation and pollution, that can alter insect physiology and immune defences. These changes may have contributed to global insect decline and the dynamics of insect-transmitted diseases. The ability of insects to mount immune responses upon infection is crucial for defence against pathogens and parasites. Suppressed immune defences reduce fitness by causing disease-driven mortality and elevated immune responses reduce energy available to invest in other fitness traits such as reproduction. Understanding the impact of anthropogenic factors on insect-pathogen interactions is therefore key to determining the contribution of anthropogenic global change to pathogen-driven global insect decline and the emergence and transmission of insect-borne diseases. Here, we synthesise evidence of the impact of anthropogenic factors on insect immunity. We found evidence that anthropogenic factors, such as insecticides and heavy metals, directly impacting insect immune responses by inhibiting immune activation pathways. Alternatively, factors such as global warming, heatwaves, elevated CO2 and landscape degradation can indirectly reduce insect immune responses via reducing the energy available for immune function. We further review how anthropogenic factors impact pathogen clearance and contribute to an increase in vector-borne diseases. We discuss the fitness cost of anthropogenic factors via pathogen-driven mortality and reduced reproductive output and how this can contribute to species extinction. We found that most research has determined the impact of a single anthropogenic factor on insect immune responses or pathogen resistance. We recommend studying the combined impact of multiple stressors on immune response and pathogen resistance to understand better how anthropogenic factors affect insect immunity. We conclude by highlighting the importance of initiatives to mitigate the impact of anthropogenic factors on insect immunity, to reduce the spread of vector-borne diseases, and to protect vulnerable ecosystems from emerging diseases.

Nucleic acid-based therapeutics have become a key pillar of the 'third wave' of modern medicine, following the eras of small molecule inhibitors and antibody drugs. Their rapid progress is heavily dependent on delivery technologies, with the development of N-acetylgalactosamine (GalNAc) conjugates marking a breakthrough in targeting liver diseases. This technology has gained significant attention for its role in addressing chronic conditions like chronic hepatitis B (CHB) and nonalcoholic steatohepatitis (NASH), which are challenging to treat with conventional methods.

This review explores the origins, mechanisms, and advantages of GalNAc-siRNA delivery systems, highlighting their ability to target hepatocytes via the asialoglycoprotein receptor (ASGPR). The literature reviewed covers preclinical and clinical advancements, particularly in CHB and NASH. Key developments in stabilization chemistry and conjugation technologies are examined, emphasizing their impact on enhancing therapeutic efficacy and patient compliance.

GalNAc-siRNA technology represents a transformative advancement in RNA interference (RNAi) therapies, addressing unmet needs in liver-targeted diseases. While significant progress has been made, challenges remain, including restricted targeting scope and scalability concerns. Continued innovation is expected to expand applications, improve delivery efficiency, and overcome limitations, establishing GalNAc-siRNA as a cornerstone for future nucleic acid-based treatments.

Delivery of exogenous nucleic acids (NAs) for gene regulation in bacteria, bypassing the barrier of the cell wall, is essential for advancing fundamental microbiology and genetic engineering, and the treatment of bacterial diseases. However, current methods that rely on electrical or chemical interventions are limited by their complexity, specialized expertise, and laboratory-specific instrumentation. This study explores the capability of gold nanoclusters (AuNCs) as carriers for delivering small-interfering RNA and antisense oligonucleotides into bacteria for targeted gene regulation while shielding them from degradation during transport. By enhancing the cytoplasmic membrane permeability, the AuNCs enable efficient internalization of NAs into both Gram-positive and Gram-negative bacteria while exerting negligible influence on bacterial activity. It is demonstrated that the rationally designed NAs can be released from the AuNCs within bacteria, enabling ~70% knockdown of mecA in Methicillin-resistant Staphylococcus aureus (MRSA). This significantly reduces MRSA's antibiotic resistance and enhances oxacillin treatment efficacy. Furthermore, the successful silencing of ligA in Escherichia coli and pilQ in Pseudomonas aeruginosa highlights the broad adaptability of the approach across diverse bacterial species. The AuNCs-based next-generation NA delivery system has the potential to transform bacterial gene regulation-previously restricted to laboratory settings-into a versatile and scalable solution for real-world application.

DNA methylation is one mechanism of epigenetic regulation in plants. Small interfering RNAs (siRNAs) targeted endogenous genes and caused the promoters to be hypermethylated, namely RNA-directed DNA methylation (RdDM). Repressor of silencing 1 (ROS1) is an active DNA demethylase involved in the regulation of DNA methylation. This study indicates that ROS1-mediated DNA demethylation plays important roles in regulating the expression of these stress response genes and in response to biotic stresses. Further experiments confirmed that the expression level of the ROS1 gene was significantly upregulated in A. thaliana plants infected with beet severe curly top virus (BSCTV). Moreover, the DNA sequencing results demonstrated that ROS1 interferes with DNA methylation of repeat regions in the promoters of ACD6, GSTF14, and ACO3 in A. thaliana plants infected with BSCTV. These findings reveal the epigenetic mechanisms by which ROS1 regulates the expression of the stress response genes, thereby improving the adaptability of plants to biotic stresses.

Bone marrow-derived mesenchymal stem cells (BM-MSCs) tend to migrate towards tumor sites and interact with tumor cells, thus incorporating into tumor microenvironment by transition into various stromal cells, particularly tumor-associated MSCs. However, the mechanisms involved in this process is still not clarified. Herein, we focused on miR-99a-5p and confirmed its reduction in gastric cancer-associated MSCs (GC-MSCs) compared to BM-MSCs. Under-expression of miR-99a-5p stimulated BM-MSCs transition into GC-MSCs-like cells, while overexpression of this miRNA abrogated tumor-promoting roles of GC-MSCs. miR-99a-5p not only targeted modulation of fibroblast growth factor receptor (FGFR3) but also negatively affected its phosphorylated levels. Suppression of FGFR3 signaling by AZD4547 or siRNA against FGFR3 notably blocked the miR-99a-5p inhibitor-induced BM-MSCs transition and the oncogenic roles of GC-MSCs. However, miR-99a-5p overexpression did not diminish the ability of gastric cancer cells to educate BM-MSCs. The levels of phosphorylated FGFR3, but not total FGFR3, was increased in BM-MSCs educated by gastric cancer cells. AZD4547 significantly suppressed the education capacity of gastric cancer cells on BM-MSCs. Taken together, although manipulating miR-99a-5p to mimic its levels in GC-MSCs promotes the transition of BM-MSCs into GC-MSCs-like cells, FGFR3 signaling, rather than miR-99a-5p, is unexpectedly essential for the education of BM-MSCs by gastric cancer cells. This discovery provides a novel mechanism underlying the transition of BM-MSCs into tumor-associated MSCs and identifies potential therapeutic targets for gastric cancer.

Viruses are a major cause of plant disease with an estimated annual economic impact of over $30 billion. They account for nearly 50% of the pathogens responsible for emerging and re-emerging plant diseases worldwide. To confer resistance against these diseases RNA interference (RNAi) technology can be employed. Designing silencing molecules like dsRNA homologous to the viral genome has been the most common non-transgenic method to induce RNAi mediated resistance in plants. dsRNAs are carefully tailored and produced considering factors such as the type of virus, target genomic region, dsRNA size, and method of application to maximise their efficiency. With the advent of new technologies like nano-platforms, a sustainable carrier can be developed to deliver these molecules, enhancing their stability and its bioavailability. This innovative technology faces regulatory debates globally and lacks legislation for commercialisation. But this is an eco-friendly alternative to conventional pesticides that can revolutionize the future of plant viral disease management, providing a bio-safe and an evergreen solution.

Understanding the epigenetic molecular mechanisms (EMMs) of reproduction is crucial for developing advanced and targeted control strategies for Spodoptera frugiperda. Differential expression analysis revealed 11 known miRNAs with varying expression levels, including nine upregulated and two downregulated miRNAs, in virgin females compared with males. The predictive analysis identified 426 target genes for these miRNAs, with ribogenesis highlighted as a key process in oogenesis and egg fertilization. This study also investigated the expression of miRNAs in both virgin and mated male and female S. frugiperda, with a focus on their roles in reproduction. A strong negative correlation was observed between miRNA expression levels and their target hub genes, confirming the transcriptional regulation by miRNAs. Additionally, protein-protein interaction (PPI) network identified the gene CG5033 (BOP1), as a central hub, was also predicted to be the target of miR-92a-3p in S. frugiperda, is involved in the maturation of large ribosomal RNA subunits. This study further provided experimental evidence that either the depletion of miR-92a-3p in virgin females or the knockdown of BOP1 in virgin males led to the production of infertile eggs post-mating. These findings validate the regulatory role of the miR-92a-3p - BOP1 interaction and underscore its importance in oogenesis and fertilization.

Huanglongbing (HLB) is a systemic disease of citrus caused by the bacterial pathogen Candidatus Liberibacter asiaticus (CLas) that limits citrus production worldwide. CLas is an obligate bacterial pathogen that multiplies in citrus trees and in the insect vector, the Asian citrus psyllid (ACP), Diaphorina citri Kuwayama. There is no cure for HLB currently and broad-spectrum antibiotics represent one possible therapeutic against disease symptoms. Single-stranded nucleic acid analogs, 2'-deoxy-2'-Fluoro-β-D-arabinonucleic antisense oligonucleotides (FANA ASOs), can modulate gene expression by enzymatic degradation or steric blocking of an RNA target. FANA ASOs recognize and bind to specific RNA forms, including mRNA, miRNA and long noncoding RNA, through complementary base-pairing.

Injection of oxytetracycline (OTC) into mature citrus trees with HLB ameliorated symptoms of disease, increased fruit yield and quality of juice as compared with that produced by noninjected controls. Injection of trees with FANA ASOs reduced CLas abundance but did not improve fruit yield and quality above control levels at the injection dosage tested. Reduced pathogen relative abundance following OTC injection was coincident with lower CLas acquisition and inoculation by laboratory deployed and wild-type D. citri collected from the field, respectively. However, injections of FANA ASOs did not consistently reduce CLas transmission as compared with noninjected controls.

Trunk injection of OTC may be useful in management of HLB by reducing CLas infection in trees and disrupting transmission. However, more research is needed to verify the potential usefulness of FANA ASOs. Optimizing FANA ASO dosage in trees and exploring the potential of multiplex FANA ASOs that simultaneously target multiple mRNAs could possibly enhance their efficacy against CLas. © 2024 Society of Chemical Industry.

Cardiovascular diseases (CVDs), such as atherosclerotic cardiovascular diseases, heart failure (HF), and acute coronary syndrome, represent a significant threat to global health and impose considerable socioeconomic burdens. The intricate pathogenesis of CVD involves various regulatory mechanisms, among which microRNAs (miRNAs) have emerged as critical posttranscriptional regulators. In particular, miR-155 has demonstrated differential expression patterns across a spectrum of CVD and is implicated in the etiology and progression of arterial disorders. This systematic review synthesizes current evidence on the multifaceted roles of miR-155 in the modulation of genes and pathological processes associated with CVD. We delineate the potential of miR-155 as a diagnostic biomarker and therapeutic target, highlighting its significant regulatory influence on conditions such as atherosclerosis, aneurysm, hypertension, HF, myocardial hypertrophy, and oxidative stress. Our analysis underscores the transformative potential of miR-155 as a target for intervention in cardiovascular medicine, warranting further investigation into its clinical applicability.

Background: In recent years, micro ribonucleic acids (miRNAs) have been recognized as key regulators in numerous biological processes, particularly in the development and progression of diseases. As a result, extensive research has focused on uncovering the critical involvement of miRNAs in disease mechanisms to better comprehend the underlying causes of human diseases. Despite these efforts, relying solely on biological experiments to identify miRNA-disease associations is both time-consuming and costly, making it an impractical approach for large-scale studies. Methods: In this paper, we propose a novel DeepWalk-based graph embedding method for predicting miRNA-disease association (DWMDA). Using DeepWalk, we extracted meaningful low-dimensional vectors from the miRNA and disease networks. Then, we applied a deep neural network to identify miRNA-disease associations using the low-dimensional vectors of miRNAs and diseases extracted via DeepWalk. Results: An ablation study was conducted to assess the proposed graph embedding modules. Furthermore, DWMDA demonstrates exceptional performance in two major cancer case studies (breast and lung), with results based on statistically robust measures, further emphasizing its reliability as a method for identifying associations between miRNAs and diseases. Conclusions: We expect that our model will not only facilitate the accurate prediction of disease-associated miRNAs but also serve as a generalizable framework for exploring interactions among various biological entities.

An increasing human population, the emergence of resistances against pesticides and their potential impact on the environment call for the development of new eco-friendly pest control strategies. RNA interference (RNAi)-based pesticides have emerged as a new option with the first products entering the market. Essentially, double-stranded RNAs targeting essential genes of pests are either expressed in the plants or sprayed on their surface. Upon feeding, pests mount an RNAi response and die. However, it has remained unclear whether RNAi-based insecticides should target the same pathways as classic pesticides or whether the different mode-of-action would favor other processes. Moreover, there is no consensus on the best genes to be targeted.

We performed a genome-wide screen in the red flour beetle to identify 905 RNAi target genes. Based on a validation screen and clustering, we identified the 192 most effective target genes in that species. The transfer to oral application in other beetle pests revealed a list of 34 superior target genes, which are an excellent starting point for application in other pests. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) analyses of our genome-wide dataset revealed that genes with high efficacy belonged mainly to basic cellular processes such as gene expression and protein homeostasis - processes not targeted by classic insecticides.

Our work revealed the best target genes and target processes for RNAi-based pest control and we propose a procedure to transfer our short list of superior target genes to other pests. © 2024 The Author(s). Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

High-throughput genetic screening serves as an indispensable approach for deciphering gene functions and the intricate relationships between phenotypes and genotypes. The CRISPR/Cas9 system, with its ability to precisely edit genomes on a large scale, has revolutionized the field by enabling the construction of comprehensive genomic libraries. This technology has become a cornerstone for genome-wide screenings in disease research. This review offers a comprehensive examination of how CRISPR/Cas9-based genetic screening has been leveraged to uncover genes that play a role in disease mechanisms, focusing on areas such as cancer development and viral replication processes. The insights presented in this review hold promise for the development of novel therapeutic strategies and precision medicine approaches.

While many genetic tools exist for zebrafish, this animal model still lacks robust gene-silencing and microRNA-delivery technologies enabling spatio-temporal control and traceability. We have recently demonstrated that engineered pri-miR backbones can trigger stable gene knockdown and/or express microRNA(s) of choice in this organism. However, this miRNA-expressing technology presents important limitations. First, to trigger potent knockdown(s), multiple synthetic-miRNAs must be expressed simultaneously, compromising the co-expression of fluorescent marker(s) and knockdown traceability. Second, when gene(s) knockdown triggers significant phenotypes, like homozygous mutants with severe early phenotypes, it is difficult, if not impossible, to maintain transgenic carriers. To solve these problems and provide a mature RNAi and microRNA-delivery technology, we have generated new RNAi reagents and an inducible delivery system based on the Cre/Lox technology. This system allows the creation of asymptomatic/silent carriers, easing the production of embryos with potent knockdowns that can be traced and spatiotemporally controlled. We further demonstrated the utility of this approach by establishing novel inducible and tissue-specific models of spinal muscular atrophy, opening new avenues for studying smn1-gene function and pathogenicity. All in all, these materials and techniques will be invaluable in studying microRNA biology and in modelling or tackling conditions in which gene dosage is key.

Background: Over the past few decades, micro ribonucleic acids (miRNAs) have been shown to play significant roles in various biological processes, including disease incidence. Therefore, much effort has been devoted to discovering the pivotal roles of miRNAs in disease incidence to understand the underlying pathogenesis of human diseases. However, identifying miRNA-disease associations using biological experiments is inefficient in terms of cost and time. Methods: Here, we discuss a novel machine-learning model that effectively predicts disease-related miRNAs using a graph convolutional neural network with neural collaborative filtering (GCNCF). By applying the graph convolutional neural network, we could effectively capture important miRNAs and disease feature vectors present in the network while preserving the network structure. By exploiting neural collaborative filtering, miRNAs and disease feature vectors were effectively learned through matrix factorization and deep learning, and disease-related miRNAs were identified. Results: Extensive experimental results based on area under the curve (AUC) scores (0.9216 and 0.9018) demonstrated the superiority of our model over previous models. Conclusions: We anticipate that our model could not only serve as an effective tool for predicting disease-related miRNAs but could be employed as a universal computational framework for inferring relationships across biological entities.

Current treatments for retinal disorders are anti-angiogenic agents, laser photocoagulation, and photodynamic therapies. These conventional treatments focus on reducing abnormal blood vessel formation in the retina, which, in a low-oxygen environment, can lead to harmful proliferation of endothelial cells. This results in dysfunctional, leaky blood vessels that cause retinal edema, hemorrhage, and vision loss. Age-related Macular Degeneration is a primary cause of vision loss and blindness in the elderly, impacting around 20% of those over 50 years old. This complex disease is also closely related to oxidative stress in retina. In this review, we explore the challenge of treating retinal diseases, alternatives and possibilities of enhancing the effectiveness of therapies using co-delivery systems containing both antiangiogenic and antioxidant therapeutic agents. Despite recent proposals potential, the lack of extensive clinical studies on the long-term outcomes and optimal combinations of therapies means that the full risk profile and effectiveness of combined therapy are not yet completely understood. These factors must be carefully considered and managed by healthcare providers to optimize treatment outcomes and ensure patient safety.

Lung cancer is a significant cause of cancer-related death worldwide. It can be broadly categorised into small-cell lung cancer (SCLC) and Non-small cell lung cancer (NSCLC). Surgical intervention, radiation therapy, and the administration of chemotherapeutic medications are among the current treatment modalities. However, the application of chemotherapy may be limited in more advanced stages of metastasis due to the potential for adverse effects and a lack of cell selectivity. Although small-molecule anticancer treatments have demonstrated effectiveness, they still face several challenges. The challenges at hand in this context comprise insufficient solubility in water, limited bioavailability at specific sites, adverse effects, and the requirement for epidermal growth factor receptor inhibitors that are genetically tailored. Bio-macromolecular drugs, including small interfering RNA (siRNA) and messenger RNA (mRNA), are susceptible to degradation when exposed to the bodily fluids of humans, which can reduce stability and concentration. In this context, nanoscale delivery technologies are utilised. These agents offer encouraging prospects for the preservation and regulation of pharmaceutical substances, in addition to improving the solubility and stability of medications. Nanocarrier-based systems possess the notable advantage of facilitating accurate and sustained drug release, as opposed to traditional systemic methodologies. The primary focus of scientific investigation has been to augment the therapeutic efficacy of nanoparticles composed of lipids. Numerous nanoscale drug delivery techniques have been implemented to treat various respiratory ailments, such as lung cancer. These technologies have exhibited the potential to mitigate the limitations associated with conventional therapy. As an illustration, applying nanocarriers may enhance the solubility of small-molecule anticancer drugs and prevent the degradation of bio-macromolecular drugs. Furthermore, these devices can administer medications in a controlled and extended fashion, thereby augmenting the therapeutic intervention's effectiveness and reducing adverse reactions. However, despite these promising results, challenges remain that must be addressed. Multiple factors necessitate consideration when contemplating the application of nanoparticles in medical interventions. To begin with, the advancement of more efficient delivery methods is imperative. In addition, a comprehensive investigation into the potential toxicity of nanoparticles is required. Finally, additional research is needed to comprehend these treatments' enduring ramifications. Despite these challenges, the field of nanomedicine demonstrates considerable promise in enhancing the therapy of lung cancer and other respiratory diseases.

Plant viruses have evolved different viral suppressors of RNA silencing (VSRs) to counteract RNA silencing which is a small RNA-mediated sequence-specific RNA degradation mechanism. Previous studies have already shown that the coat protein (CP) of cucumber mosaic virus (CMV) reduced RNA silencing suppression (RSS) activity of the VSR of CMV, the 2b protein. To demonstrate the universality of this CP-VSR interference, our study included three different viruses: CMV and peanut stunt virus (PSV) from the Bromoviridae, and plum pox virus (PPV) from the Potyviridae family. The RSS activity of the three VSRs (CMV 2b, PSV 2b, and PPV HC-Pro) was compared using Agrobacterium-mediated transient expression in Nicotiana benthamiana and the effect of CMV CP, PSV CP and PPV CP was validated on the RSS activity of their cognate and heterologous VSRs as well. Furthermore, the VSRs were also evaluated in PTGS suppressor-deficient CMV mutant (CMV NVE/10-12/AAA) virus-infected plants. The joint presence of CPs and VSRs resulted in decreased RSS activity in each combination, regardless of the origin of the two proteins, suggesting a universal role of the viral CPs in fine tuning of RSS. Interestingly the PSV CP elicited the strongest negative effect on the RSS activity of all three VSRs.

The occurrence of multiple primary cancers in individual patients underscores the need for diagnostic and therapeutic techniques with augmented cancer-targeting selectivity and broad-spectrum antitumor effects. To address this, we develop a quadruple-input-triggered OR-AND-AND logic gated oncological nanosystem (OAA). This system employs four cancer-related markers (EpCAM, MUC1, APE1, and miR-21) to generate three distinct fluorescence signals, enabling precise differentiation of various cancer cell lines (MCF-7, HepG2, and HeLa) from normal cells (MCF-10A). Additionally, the OAA system integrates photodynamic therapy (PDT) and gene silencing strategies, allowing selective activation of Ce6 release, miR-21 gene silencing, and VEGFR2 mRNA gene silencing through the OR-AND-AND logic gating mechanism in a cancer-specific manner. This synergetic therapeutic approach induces significant apoptosis in multiple cancer cell lines while sparing normal cells, demonstrating improved cancer-targeting specificity and broad-spectrum versatility. This intelligent platform precisely types and treats diverse cancer cells, powering the future exploration of advanced diagnostic and therapeutic strategies to combat highly heterogeneous diseases.

Double-stranded RNA (dsRNA) has emerged as key player in gene silencing for the past two decades. Tailor-made dsRNA is now recognized a versatile raw material, suitable for a wide range of applications in biopesticide formulations, including insect control to pesticide resistance management. The mechanism of RNA interference (RNAi) acts at the messenger RNA (mRNA) level, utilizing a sequence-dependent approach that makes it unique in term of effectiveness and specificity compared to conventional agrochemicals. Two primary categories of small RNAs, known as short interfering RNAs (siRNAs) and microRNAs (miRNAs), function in both somatic and germline lineages in a broad range of eukaryotic species to regulate endogenous genes and to defend the genome from invasive nucleic acids. Furthermore, the application of RNAi in crop protection can be achieved by employing plant-incorporated protectants through plant transformation, but also by non-transformative strategies such as the use of formulations of sprayable RNAs as direct control agents, resistance factor repressors or developmental disruptors. This review explores the agricultural applications of RNAi, delving into its successes in pest-insect control and considering its broader potential for managing plant pathogens, nematodes, and pests. Additionally, the use of RNAi as a tool for addressing pesticide-resistant weeds and insects is reviewed, along with an evaluation of production costs and environmental implications.

Hematological disorders result in significant health consequences, and traditional therapies frequently entail adverse reactions without addressing the root cause. A potential solution for hematological disorders characterized by gain-of-function mutations lies in the emergence of small interfering RNA (siRNA) molecules as a therapeutic option. siRNAs are a class of RNA molecules composed of double-stranded RNAs that can degrade specific mRNAs, thereby inhibiting the synthesis of underlying disease proteins. Therapeutic interventions utilizing siRNA can be tailored to selectively target genes implicated in diverse hematological disorders, including sickle cell anemia, β-thalassemia, and malignancies such as lymphoma, myeloma, and leukemia. The development of efficient siRNA silencers necessitates meticulous contemplation of variables such as the RNA backbone, stability, and specificity. Transportation of siRNA to specific cells poses a significant hurdle, prompting investigations of diverse delivery approaches, including chemically modified forms of siRNA and nanoparticle formulations with various biocompatible carriers. This review delves into the crucial role of siRNA technology in targeting and treating hematological malignancies and disorders. It sheds light on the latest research, development, and clinical trials, detailing how various pharmaceutical approaches leverage siRNA against blood disorders, mainly concentrating on cancers. It outlines the preferred molecular targets and physiological barriers to delivery while emphasizing the growing potential of various therapeutic delivery methods. The need for further research is articulated in the context of overcoming the shortcomings of siRNA in order to enrich discussions around siRNA's role in managing blood disorders and aiding the scientific community in advancing more targeted and effective treatments.

Sjögren's syndrome (SS) is an autoimmune disease that can be classified as an epithelitis based on the immune-mediated attack directed specifically at epithelial cells. SS predominantly affects women, is characterized by the production of highly specific circulating autoantibodies, and the major targets are the salivary and lachrymal glands. Although a genetic predisposition has been amply demonstrated for SS, the etiology remains unclear. The recent integration of epigenetic data relating to autoimmune diseases opens new therapeutic perspectives based on a better understanding of the molecular processes implicated. In the autoimmune field, non-coding RNA molecules (nc-RNA), which regulate gene expression by binding to mRNAs and could have a therapeutic value, have aroused great interest. The focus of this review is to summarize the biological functions of nc-RNAs in the pathogenesis of SS and decode molecular pathways implicated in the disease, in order to identify new therapeutic strategies.

Metabolism-disorder-induced liver diseases have become increasingly prevalent worldwide and are clinically linked to obesity and type 2 diabetes. In addition, a large number of previous literature studies have indicated that plasma miR-130b is a promising biomarker for the early diagnosis and treatment of obesity. However, whether miRNA-130b that was positively correlated with obesity resulted in hepatic inflammation needs to be further studied. Therefore, the study aims to determine the effect of microvesicle-shuttled miRNA-130b (miR-130b-MV) on the hepatic inflammation and its potential mechanism in high-fat diet-induced obese mice. Three-week-old C57BL/6 mice were fed a high-fat diet for eight weeks. Then, the obese mice received tail vein injections of MV-packaged scrambled control microRNA (miR-SC-MV) or miR-130b-MV every other day for 10 days. Compared with the control group, the miR-130b-MV injection significantly reduced the body weight while increasing the ratio of liver wet weight to total body weight. In addition, the miR-130b-MV injection significantly activated the hepatic inflammation by increasing the expression of proinflammatory genes, although the plasma concentrations of IL-6 and TNF-α were only slightly increased. Furthermore, the miR-130b-MV injection significantly increased the hepatic miR-130b expression while significantly suppressing the protein expression and phosphorylation of GR, a potential target of miR-130b. Moreover, the miR-130b overexpression results in a decrease in the expression of endogenous GR protein and a decrease in the activity of the luciferase reporter of GR 3'-UTR. In addition, the miR-130b-MV injection significantly upregulated NF-kB (p50) in both the cytoplasm and nucleus, showing enhanced proinflammation response. The above results demonstrated that miR-130b-MV activated the hepatic inflammation by inhibiting GR-mediated immunosuppression in high-fat diet-induced obese mice, suggesting a novel mechanism underlying the obesity-induced hepatic inflammation, and the inhibition of miR-130b may serve as a new molecular therapeutic target for the prevention and treatment of hepatic inflammation.

Modulating the expression of a coding or noncoding gene is a key tool in scientific research. This strategy has evolved methodologically due to advances in cloning approaches, modeling/algorithms in short hairpin RNA (shRNA) design for knockdown efficiency, and biochemical modifications in RNA synthesis, among other developments. Overall, these modifications have improved the ways to either reduce or induce the expression of a given gene with efficiency and facility for implementation in the lab. Allied with that, the existence of various human cell line models for cancer covering different histotypes and biological behaviors, especially for thyroid cancer, has helped improve the understanding of cancer biology. In this review, we cover the most frequently used current techniques for gene modulation in the thyroid cancer field, such as RNA interference (RNAi), short hairpin RNA (shRNA), and gene editing with CRISPR/Cas9 for inhibiting a target gene, and strategies to overexpress a gene, such as plasmid cloning and CRISPRa. Exploring the possibilities for gene modulation allows the improvement of the scientific quality of the studies and the integration of clinicians and basic scientists, leading to better development of translational research.

Ribonucleic acid (RNA) undergoes dynamic changes in its structure and function under various intracellular and extracellular conditions over time. However, there is a lack of research on the concept of the RNA age to describe its diverse fates. This study proposes a definition of RNA age to address this issue. RNA age was defined as a sequence of numbers wherein the elements in the sequence were the nucleotide ages of the ribonucleotide residues in the RNA. Mean nucleotide age was used to represent RNA age. This definition describes the temporal properties of RNAs that have undergone diverse life histories and reflects the dynamic state of each ribonucleotide residue, which can be expressed mathematically. Notably, events (including base insertions, base deletions, and base substitutions) are likely to cause RNA to become younger or older when using mean nucleotide ages to represent the RNA age. Although information, including the presence of added markers in RNA, chemical modification structure of the RNA, and the excision of introns in the mRNA in cells, may provide a basis for identifying RNA age, little is known about determining the RNA age of extracellular RNA in the wild. Nonetheless, we believe that RNA age has an important relationship with the diverse biological properties of RNA under intracellular and extracellular conditions. Therefore, our proposed definition of RNA age offers new perspectives for studying dynamic changes in RNA function, RNA aging, ancient RNA, environmental RNA, and the ages of other biomolecules.

While Dicer plays an important antiviral role through the RNAi pathway in plants and invertebrates, its contribution to antiviral immunity in vertebrates and more specifically mammals is more controversial. The apparent limited RNAi activity in mammalian cells has been attributed to the reduced long dsRNA processive activity of mammalian Dicer, as well as a functional incompatibility between the RNAi and IFN pathways. Why Dicer has lost this antiviral activity in the profit of the IFN pathway is still unclear. We propose that the primary direct antiviral activity of Dicer has been functionally replaced by other sensors in the IFN pathway, leading to its specialization toward microRNA maturation. As a result, Dicer can regulate the innate immune response and prevent basal activation of the IFN pathway in mammals. Here, we discuss this hypothesis, highlighting how the adaptation of the helicase domain of mammalian Dicer may be key to this process.

The RNA interference (RNAi) efficiency of double-stranded RNA (dsRNA) delivery to insects by various methods is different and the reduced efficacy of feeding dsRNA is partly due to the presence of DNA/RNA non-specific endonuclease in the insect gut. However, the mechanism leading to the low RNAi efficiency of Nilaparvata lugens by feeding remains elusive.

In this study, we identified a putatively DNA/RNA non-specific endonuclease gene in the N. lugens genome database that was highly expressed in the first nymphal instar and the midgut. Different expression levels of NldsRNase after feeding and injection suggested that NldsRNase might interfere with oral RNAi in N. lugens. A co-delivery RNAi strategy further revealed that the presence of NldsRNase reduces RNAi efficiency. In vitro dsRNA degradation experiments also showed that the stability of dsRNA was higher in a gut mixture from nymphs injected with dsNldsRNase. These results support the idea that the low oral RNAi response observed in N. lugens is likely due to the presence of NldsRNase.

Our study provides insight into the differences in RNAi response between the injection and feeding of dsRNA in N. lugens and sheds light on the mechanisms underlying the reduced efficacy of RNAi via feeding. These findings may help to inform the development of more-effective RNAi-based strategies controlling N. lugens and other insect pests. © 2024 Society of Chemical Industry.

Antibiotic resistance is a critical global health concern, causing millions of prolonged bacterial infections every year and straining our healthcare systems. Novel antibiotic strategies are essential to combating this health crisis and bacterial non-coding RNAs are promising targets for new antibiotics. In particular, a class of bacterial non-coding RNAs called riboswitches has attracted significant interest as antibiotic targets. Riboswitches reside in the 5'-untranslated region of an mRNA transcript and tune gene expression levels in cis by binding to a small-molecule ligand. Riboswitches often control expression of essential genes for bacterial survival, making riboswitch inhibitors an exciting prospect for new antibacterials. Synthetic ligand mimics have predominated the search for new riboswitch inhibitors, which are designed based on static structures of a riboswitch's ligand-sensing aptamer domain or identified by screening a small-molecule library. However, many small-molecule inhibitors that bind an isolated riboswitch aptamer domain with high affinity in vitro lack potency in vivo. Importantly, riboswitches fold and respond to the ligand during active transcription in vivo. This co-transcriptional folding is often not considered during inhibitor design, and may explain the discrepancy between a low Kd in vitro and poor inhibition in vivo. In this review, we cover advances in riboswitch co-transcriptional folding and illustrate how intermediate structures can be targeted by antisense oligonucleotides-an exciting new strategy for riboswitch inhibitor design.

RNA interference (RNAi) stands as a widely employed gene interference technology, with small interfering RNA (siRNA) emerging as a promising tool for cancer treatment. However, the inherent limitations of siRNA, such as easy degradation and low bioavailability, hamper its efficacy in cancer therapy. To address these challenges, this study focused on the development of a nanocarrier system (HLM-N@DOX/R) capable of delivering both siRNA and doxorubicin for the treatment of breast cancer.

The study involved a comprehensive investigation into various characteristics of the nanocarrier, including shape, diameter, Fourier transform infrared (FT-IR) spectroscopy, X-ray photoelectron spectroscopy (XPS), encapsulation efficiency, and drug loading. Subsequently, in vitro and in vivo studies were conducted on cytotoxicity, cellular uptake, cellular immunofluorescence, lysosome escape, and mouse tumor models to evaluate the efficacy of the nanocarrier in reversing tumor multidrug resistance and anti-tumor effects.

The results showed that HLM-N@DOX/R had a high encapsulation efficiency and drug loading capacity, and exhibited pH/redox dual responsive drug release characteristics. In vitro and in vivo studies showed that HLM-N@DOX/R inhibited the expression of P-gp by 80%, inhibited MDR tumor growth by 71% and eliminated P protein mediated multidrug resistance.

In summary, HLM-N holds tremendous potential as an effective and targeted co-delivery system for DOX and P-gp siRNA, offering a promising strategy for overcoming MDR in breast cancer.

The foundation of most food production systems underpinning global food security is the careful management of soil resources. Embedded in the concept of soil health is the impact of diverse soil-borne pests and pathogens, and phytoparasitic nematodes represent a particular challenge. Root-knot nematodes and cyst nematodes are severe threats to agriculture, accounting for annual yield losses of US$157 billion. The control of soil-borne phytoparasitic nematodes conventionally relies on the use of chemical nematicides, which can have adverse effects on the environment and human health due to their persistence in soil, plants, and water. Nematode-resistant plants offer a promising alternative, but genetic resistance is species-dependent, limited to a few crops, and breeding and deploying resistant cultivars often takes years. Novel approaches for the control of phytoparasitic nematodes are therefore required, those that specifically target these parasites in the ground whilst minimizing the impact on the environment, agricultural ecosystems, and human health. In addition to the development of next-generation, environmentally safer nematicides, promising biochemical strategies include the combination of RNA interference (RNAi) with nanomaterials that ensure the targeted delivery and controlled release of double-stranded RNA. Genome sequencing has identified more than 75 genes in root knot and cyst nematodes that have been targeted with RNAi so far. But despite encouraging results, the delivery of dsRNA to nematodes in the soil remains inefficient. In this review article, we describe the state-of-the-art RNAi approaches targeting phytoparasitic nematodes and consider the potential benefits of nanotechnology to improve dsRNA delivery.

Small molecules (SMs) play a pivotal role in regulating microRNAs (miRNAs). Existing prediction methods for associations between SM-miRNA have overlooked crucial aspects: the incorporation of local topological features between nodes, which represent either SMs or miRNAs, and the effective fusion of node features with topological features. This study introduces a novel approach, termed high-order topological features for SM-miRNA association prediction (HTFSMMA), which specifically addresses these limitations. Initially, an association graph is formed by integrating SM-miRNA association data, SM similarity, and miRNA similarity. Subsequently, we focus on the local information of links and propose target neighborhood graph convolutional network for extracting local topological features. Then, HTFSMMA employs graph attention networks to amalgamate these local features, thereby establishing a platform for the acquisition of high-order features through random walks. Finally, the extracted features are integrated into the multilayer perceptron to derive the association prediction scores. To demonstrate the performance of HTFSMMA, we conducted comprehensive evaluations including five-fold cross-validation, leave-one-out cross-validation (LOOCV), SM-fixed local LOOCV, and miRNA-fixed local LOOCV. The area under receiver operating characteristic curve values were 0.9958 ± 0.0024 (0.8722 ± 0.0021), 0.9986 (0.9504), 0.9974 (0.9111), and 0.9977 (0.9074), respectively. Our findings demonstrate the superior performance of HTFSMMA over existing approaches. In addition, three case studies and the DeLong test have confirmed the effectiveness of the proposed method. These results collectively underscore the significance of HTFSMMA in facilitating the inference of associations between SMs and miRNAs.

Malaria is a life-threatening disease caused by parasites from the genus Plasmodium. Five species can cause malaria in humans, with Plasmodium vivax being the most common in many countries and Plasmodium falciparum having the highest lethality, which can lead to cerebral malaria. Extracellular vesicles (EVs) are in focus in malaria research to better understand pathogenesis, diagnosis, therapy, and prognosis. Malaria-causing parasites use EVs to transfer their molecules to host cells, a mechanism that significantly contributes to parasite survival and successful infection. EVs have thus emerged as an essential component of the immunopathological cascade of malaria, playing a pivotal role in disease progression and severity. This chapter discusses the epidemiology and pathogenesis of malaria and the role of EVs as new diagnostic and therapeutic tools, emphasizing their potential clinical significance.

Colorectal cancer (CRC) ranks as the third most common cancer and the second leading cause of cancer-related deaths. According to clinical diagnosis and treatment, liver metastasis occurs in approximately 50 % of CRC patients, indicating a poor prognosis. The unique immune tolerance of the liver fosters an immunosuppressive tumor microenvironment (TME). In the context of tumors, numerous membrane and secreted proteins have been linked to tumor immune evasion as immunomodulatory molecules, but much remains unknown about how these proteins contribute to immune evasion in colorectal cancer liver metastasis (CRLM). This article reviews recently discovered membrane and secreted proteins with roles as both immunostimulatory and immunosuppressive molecules within the TME that influence immune evasion in CRC primary and metastatic lesions, particularly their mechanisms in promoting CRLM. This article also addresses screening strategies for identifying proteins involved in immune evasion in CRLM and provides insights into potential protein targets for treating CRLM.

In recent years, therapeutic siRNA projects are booming in the biotech and pharmaceutical industries. As these drugs act by silencing the target gene expression, a critical step is the binding of antisense strands of siRNA to RNA-induced silencing complex (RISC) and then degrading their target mRNA. However, data that we recently obtained suggest that double-stranded siRNA can also load to RISC. This brings a new understanding of the mechanism of RISC loading which may have a potential impact on how quantification of RISC loaded siRNA should be performed. By combining RNA immune precipitation and probe-based hybridization LC-fluorescence approach, we have developed a novel assay that can accurately quantify the RISC-bound antisense strand, irrespective of which form (double-stranded or single-stranded) is loaded on RISC. In addition, this novel assay can discriminate between the 5'-phosphorylated antisense (5'p-AS) and the nonphosphorylated forms, therefore specifically quantifying the RISC bound 5'p-AS. In comparison, stem-loop qPCR assay does not provide discrimination and accurate quantification when the oligonucleotide analyte exists as a mixture of double and single-stranded forms. Taking together, RISC loading assay with probe-hybridization LC-fluorescence technique would be a more accurate and specific quantitative approach for RISC-associated pharmacokinetic assessment.

The RNA world is wide, and besides mRNA, there is a variety of other RNA types, such as non-coding (nc)RNAs, which harbor various intracellular regulatory functions. This review focuses on small interfering (si)RNA and micro (mi)RNA, which form a complex network regulating mRNA translation and, consequently, gene expression. In fact, these RNAs are critically involved in the function and phenotype of all cells in the human body, including malignant cells. In cancer, the two main targets for therapy are dysregulated cancer cells and dysfunctional immune cells. To exploit the potential of mi- or siRNA therapeutics in cancer therapy, a profound understanding of the regulatory mechanisms of RNAs and following targeted intervention is needed to re-program cancer cells and immune cell functions in vivo. The first part focuses on the function of less well-known RNAs, including siRNA and miRNA, and presents RNA-based technologies. In the second part, the therapeutic potential of these technologies in treating cancer is discussed, with particular attention on manipulating tumor-associated immune cells, especially tumor-associated myeloid cells.

RNA uptake by cells is critical for RNA-mediated gene interference (RNAi) and RNA-based therapeutics. In Caenorhabditis elegans, RNAi is systemic as a result of SID-1-mediated double-stranded RNA (dsRNA) across cells. Despite the functional importance, the underlying mechanisms of dsRNA internalization by SID-1 remain elusive. Here we describe cryogenic electron microscopy structures of SID-1, SID-1-dsRNA complex and human SID-1 homologs SIDT1 and SIDT2, elucidating the structural basis of dsRNA recognition and import by SID-1. The homodimeric SID-1 homologs share conserved architecture, but only SID-1 possesses the molecular determinants within its extracellular domains for distinguishing dsRNA from single-stranded RNA and DNA. We show that the removal of the long intracellular loop between transmembrane helix 1 and 2 attenuates dsRNA uptake and systemic RNAi in vivo, suggesting a possible endocytic mechanism of SID-1-mediated dsRNA internalization. Our study provides mechanistic insights into dsRNA internalization by SID-1, which may facilitate the development of dsRNA applications based on SID-1.

A considerable proportion of the eukaryotic genome undergoes transcription, leading to the generation of noncoding RNA molecules that lack protein-coding information and are not subjected to translation. These noncoding RNAs (ncRNAs) are well recognized to have essential roles in several biological processes. Long noncoding RNAs (lncRNAs) represent the most extensive category of ncRNAs found in the human genome. Much research has focused on investigating the roles of cis-acting lncRNAs in the regulation of specific target gene expression. In the majority of instances, the regulation of sense gene expression by its corresponding antisense pair occurs in a negative (discordant) manner, resulting in the suppression of the target genes. The notion that a negative correlation exists between sense and antisense pairings is, however, not universally valid. In fact, several recent studies have reported a positive relationship between corresponding cis antisense pairs within plants, budding yeast, and mammalian cancer cells. The positive (concordant) correlation between anti-sense and sense transcripts leads to an increase in the level of the sense transcript within the same genomic loci. In addition, mechanisms such as altering chromatin structure, the formation of R loops, and the recruitment of transcription factors can either enhance transcription or stabilize sense transcripts through their antisense pairs. The primary objective of this work is to provide a comprehensive understanding of both aspects of antisense regulation, specifically focusing on the positive correlation between sense and antisense transcripts in the context of eukaryotic gene expression, including its implications towards cancer progression. This article is categorized under: RNA Processing > 3' End Processing Regulatory RNAs/RNAi/Riboswitches > Regulatory RNAs.

Animals from all major clades have evolved a segmented trunk, reflected in the human spine or the insect segments. These units emerge during embryogenesis from a posterior segment addition zone (SAZ), where repetitive gene activity is regulated by a mechanism described by the clock and wavefront/speed gradient model. In the red flour beetle Tribolium castaneum, RNA interference (RNAi) has been used to continuously knock down the function of primary pair-rule genes (pPRGs), caudal or Wnt pathway components, which has led to the complete breakdown of segmentation. However, it has remained untested, if this breakdown was reversible by bringing the missing gene function back to the system. To fill this gap, we established a transgenic system in T. castaneum, which allows blocking an ongoing RNAi effect with temporal control by expressing a viral inhibitor of RNAi via heat shock. We show that the T. castaneum segmentation machinery was able to reestablish after RNAi targeting the pPRGs Tc-eve, Tc-odd, and Tc-runt was blocked. However, we observed no rescue after blocking RNAi targeting Wnt pathway components. We conclude that the insect segmentation system contains both robust feedback loops that can reestablish and labile feedback loops that break down irreversibly. This combination may reconcile conflicting needs of the system: Labile systems controlling initiation and maintenance of the SAZ ensure that only one SAZ is formed. Robust feedback loops confer developmental robustness toward external disturbances.

Type I interferons (IFN-Is) are pivotal in innate immunity against human immunodeficiency virus I (HIV-1) by eliciting the expression of IFN-stimulated genes (ISGs), which encompass potent host restriction factors. While ISGs restrict the viral replication within the host cell by targeting various stages of the viral life cycle, the lesser-known IFN-repressed genes (IRepGs), including RNA-binding proteins (RBPs), affect the viral replication by altering the expression of the host dependency factors that are essential for efficient HIV-1 gene expression. Both the host restriction and dependency factors determine the viral replication efficiency; however, the understanding of the IRepGs implicated in HIV-1 infection remains greatly limited at present. This review provides a comprehensive overview of the current understanding regarding the impact of the RNA-binding protein families, specifically the two families of splicing-associated proteins SRSF and hnRNP, on HIV-1 gene expression and viral replication. Since the recent findings show specifically that SRSF1 and hnRNP A0 are regulated by IFN-I in various cell lines and primary cells, including intestinal lamina propria mononuclear cells (LPMCs) and peripheral blood mononuclear cells (PBMCs), we particularly discuss their role in the context of the innate immunity affecting HIV-1 replication.

Worldwide, osteoarthritis (OA) is the most common cause of joint pain in older people. Many factors contribute to osteoarthritis' development and progression, including secondary osteoarthritis' underlying causes. It is important to note that osteoarthritis affects all four tissues: cartilage, bone, joint capsule, and articular apparatus. An increasingly prominent area of research in osteoarthritis regulation is microRNAs (miRNAs), a small, single-stranded RNA molecule that controls gene expression in eukaryotes. We aimed to assess and summarize current knowledge about the mechanisms of the action of miRNAs and their clinical significance. Osteoarthritis (OA) is affected by the interaction between miRNAs and inflammatory processes, as well as cartilage metabolism. MiRNAs also influence cartilage cell apoptosis, contributing to the degradation of the cartilage in OA. Studies have shown that miRNAs may have both an inhibitory and promoting effect on osteoporosis progression through their influence on molecular mechanisms. By identifying these regulators, targeted treatments for osteoarthritis may be developed. In addition, microRNA may also serve as a biomarker for osteoarthritis. By using these biomarkers, the disease could be detected faster, and early intervention can be instituted to prevent mobility loss and slow deterioration.