Our Previous research revealed significant differences in exosome-mediated intercellular miR-425a-5p between normal children and those with fulminant myocarditis. We sought to elucidate the molecular underpinnings and functional implications of miR-425a-5p in the context of myocarditis progression.

Bioinformatics techniques were employed to predict NRAS as the target gene of miR-425a-5p. We constructed a cellular myocarditis paradigm through LPS-mediated provocation of AC16 cardiomyocyte cultures. MiR-425a-5p was overexpressed, and the expressions of NRAS, cell apoptosis, and proinflammatory cytokine profiles, encompassing IL-1β, IL-6, and TNF-α, were comprehensively quantified. An experimental autoimmune myocarditis (EAM) mouse model was created using adeno-associated virus (AAV) for miR-425a-5p overexpression. Comprehensive histopathological analyses were conducted utilizing multiple staining techniques, including hematoxylin-eosin (HE), immunohistochemical, and Masson trichrome methodologies to characterize tissue responses.

The study demonstrated that miR-425a-5p alleviated the inflammatory response in both AC16 cells and EAM mice through NRAS mediation. Single-cell data analysis of cardiac immune cells revealed that miR-425a-5p promoted Treg cell differentiation and improved cardiac function.

MiR-425a-5p plays a crucial role in modulating inflammatory responses in myocarditis, potentially offering a novel therapeutic strategy for managing the disease.

MiR-425 is a biological molecule that has potential applications in cardiovascular diseases. It can regulate biological functions by combining with LncRNAs, binding with proteins, and changing the differentiation of immune cells. MiR-425 also has a role as a biomarker of disease. In cardiovascular diseases, it has clinical significance in reducing inflammation and heart repair, inducing angiogenesis, improving the prediction of atherosclerosis, reducing cardiac fibrosis, and regulating atrial natriuretic peptide to affect cardiovascular function. Target gene prediction and KEGG enrichment analysis are also mentioned.

Interferons (IFNs) are indispensable innate antiviral cytokines that orchestrate the vertebrate immune response against viral incursions. Nearly every cell possesses the remarkable ability to release IFNs upon detecting viral threats, triggering a robust signaling cascade that alerts neighboring cells and halts viral propagation via paracrine communication. The intricate influence of IFNs is mediated by an extensive network of proteins activated through the Jak-STAT pathways, facilitating the swift transcription of over 300 interferon-stimulated genes (ISGs) that fortify cellular defenses against replication. However, the cunning nature of viruses has led to the evolution of sophisticated evasion strategies, notably through the manipulation of host microRNAs (miRNAs) that disrupt vital components of the IFN signaling machinery. This review delves into the intricate interplay between viral infections and both host- and viral-derived miRNAs, exploring their potent roles in modulating RIG-I-like receptors, Toll-like receptors, IFN receptors, and the JAK/STAT pathway, ultimately shaping the landscape of antiviral immunity.

Alzheimer's disease (AD) is a neurodegenerative disease and the most common cause of dementia, contributing to around 60-80% of cases. The main pathophysiology of AD is characterized by an abnormal accumulation of protein aggregates extracellularly (beta-amyloid plaques) and intracellularly (neurofibrillary tangles of hyperphosphorylated tau). However, an increasing number of studies have also suggested neuroinflammation may have a crucial role in precipitating the cascade reactions that result in the development of AD neuropathology. In particular, several studies indicate microRNAs (miRNAs) can act as regulatory factors for neuroinflammation in AD, with potential to affect the occurrence and/or progression of AD inflammation by targeting the expression of multiple genes. Therefore, miRNAs may have potential as therapeutic targets for AD, which requires more research. This article will review the existing studies on miRNAs that have been identified to regulate neuroinflammation, aiming to gain further insights into the specific regulatory processes of miRNAs, highlight the diagnostic and therapeutic potential of miRNAs as biomarkers in AD, as well as current challenges, and suggest the further work to bridge the gap in knowledge to utilize miRNAs as therapeutic targets for AD.

The development of drugs to accelerate wound healing is an important area of clinical research. Recent advancements have highlighted the prospects of microRNAs as therapeutic targets for various disorders, although their involvement in mice wound healing remains unclear. Peptides have been proved to be unique and irreplaceable molecules in the elucidation of competing endogenous RNAs mechanisms (ceRNA) involved with skin wound healing. In the present work, CyRL-QN15, a peptide characterized by its minimal length and maximal wound healing efficacy, was applied as a probe to explore the ceRNA mechanism in regard to accelerated wound healing. Results showed that the use of CyRL-QN15 significantly reduced the expression of miRNA-365-2-5p at the wound in mice. In mouse keratinocytes, miRNA-365-2-5p inhibition increased SIRT1 and FOXO1 protein expression and decreased STAT2 protein expression, promoting cell proliferation, migration, and reducing inflammatory factors. Similarly, inhibiting miRNA-365-2-5p at mouse wounds promoted Full-thickness injured skin wounds healing, increased SIRT1 and FOXO1 protein expression, decreased STAT2 protein expression, and reduced inflammatory factors. Overall, these findings demonstrate that miRNA-365-2-5p serves a crucial function in the biological processes underlying cutaneous wound healing in mice, offering a novel target for future therapeutic interventions in wound healing.

MiRNA-133a is a marker for the early diagnosis of acute myocardial infarction. Specific detection of miRNA-133a is of great significance for early diagnosis and treatment of heart disease. Here, a cascade amplification strategy based on entropy-driven DNA circuit (EDC) and rolling circle transcription (RCT) was constructed to generate repeated fluorescent light-up RNA aptamers for one-pot, and label-free detection of miRNA-133a. In this study, target miRNA-initiated EDC to produce single-stranded DNA would allow for the ligation of RCT's padlock into a loop and the formation of the complete T7 promoter. Subsequently the RCT was triggered, and effectively generated large number of repeated Spinach sequences. The aptamer combined with the corresponding fluorophore DFHBI-1T and formed RNA aptamer-fluorophore complexes to generate enhanced fluorescence signals. The developed biosensor exhibits sensitive detection of miRN-133a, with a linear range of 50 pM to 50 nM and a detection limit of 38.3 pM. The recovery of the actual sample was 99.1 %-103.0 %, and the relative standard deviation (RSD) was 1.6 %-3.6 %. In addition, the detection has high selectivity and can distinguish RNA sequences with single base mutation. This work provides a general method for the sensitive detection of miRNA biomarkers in molecular diagnosis.

Sepsis is a highly dangerous and complex condition that can result in death. It is characterized by a strong reaction to an infection, causing dysfunction in multiple bodily systems and a high risk of mortality. The transformation of macrophages is a vital stage in the procedure as they possess the capability to interchange between two separate types: M1, which promotes inflammation, and M2, which inhibits inflammation. The choice greatly affects the immune response of the host. This analysis underscores the rapidly expanding roles of exosomes and microRNAs (miRNAs) in regulating the trajectory of macrophage polarization during episodes of sepsis. Exosomes, extremely small extracellular vesicles, facilitate cellular communication by transferring biologically active compounds, including miRNAs, proteins, and lipids. We investigate the impact of changes in exosome production and composition caused by sepsis on macrophage polarization and function. Unique microRNAs present in exosomes play a significant role in controlling crucial signaling pathways that govern the phenotype of macrophages. Through thorough examination of recent progress in this area, we clarify the ways in which miRNAs derived from exosomes can either aggravate or alleviate the inflammatory reactions that occur during sepsis. This revelation not only deepens our comprehension of the underlying mechanisms of sepsis, but it also reveals potential new biomarkers and targets for treatment. This assessment aims to amalgamate diverse research investigations and propose potential avenues for future investigations on the influence that exosomes and miRNAs have on macrophage polarization and the body's response to sepsis. These entities are essential for controlling the host's reaction to sepsis and hold important functions in this mechanism.

MicroRNAs (miRNAs) are small, non-coding RNA molecules that play a pivotal role in the post-transcriptional regulation of gene expression. Over the past decade, they have emerged as key regulators in cancer progression, influencing different cellular processes such as proliferation, apoptosis, metastasis, and immune evasion. Their unique ability to target multiple genes simultaneously makes miRNAs highly attractive as potential therapeutic agents in oncology. However, several challenges have hindered their direct clinical application, most notably their inherent instability in biological fluids, rapid degradation by nucleases, and inefficient delivery to specific tumor sites. Additionally, off-target effects and the potential for toxicity further complicate the therapeutic use of miRNAs. Nanomedicine offers a promising solution to these challenges by enabling the development of advanced platforms for the stable, safe, and targeted delivery of miRNAs. Nanoparticle-based delivery systems, such as liposomes, polymeric nanoparticles, and inorganic nanocarriers, can protect miRNAs from degradation, improve their bioavailability, and allow for precise tumor targeting through passive or active targeting mechanisms. These nanocarriers can also be engineered to release miRNAs in response to specific stimuli within the tumor microenvironment, enhancing therapeutic efficacy while minimizing side effects. This review will explore the integration of miRNAs with nanotechnology, focusing on various nanoparticle formulations and their roles in enhancing miRNA stability, specificity, and function in cancer treatment. In addition, we will discuss current advances in preclinical and clinical applications, highlight promising tumor-targeting strategies, and address the remaining challenges such as toxicity, immunogenicity, and scalability. Future research should focus on overcoming these barriers, ultimately paving the way for the widespread adoption of personalized miRNA-based nanomedicine in cancer therapy.

Hepatitis B virus-associated chronic acute liver failure (HBV-ACLF) is the leading cause of ACLF, affecting approximately 90% of patients with ACLF. The objective of this study was to investigate the clinical relevance of miR-126-3p on HBV-ACLF as well as the regulatory impact of ERRFI1 and miR-126-3p on the inflammatory response caused by ACLF via in vitro experimental methodologies. RT-qPCR was utilized to quantify the expression levels of miR-126-3p, ERRFI1, NLRP3, caspase 1, and IL-1β. The clinical function of miR-126-3p was assessed using ROC analysis or Kaplan-Meier curve. Cell proliferation was quantified via the CCK-8 assay, while the dual-luciferase reporter assay was employed to confirm the specific binding interaction between miR-126-3p and ERRFI1. In patients with HBV-ACLF, a significant downregulation of miR-126-3p expression was observed; The level of miR-126-3p served as a prognostic indicator for the progression of HBV-ACLF, with reduced expression being associated with an unfavorable clinical outcome. In addition, miR-126-3p was found to modulate LPS-induced cell proliferation, and inflammation in THLE-2 cells through the regulation of ERRFI1 expression. Therefore, miR-126-3p might serve as a biomarker for HBV-ACLF.

Although anti-microRNA (miRNA) is capable of silencing target miRNA and regulating multiple mRNAs in diverse signaling pathways, RNA medicines still encounter numerous challenges, especially in terms of poor delivery, inefficient endo/lysosomal escape, and suboptimal treatment. Herein, we have developed a carrier-free supramolecular nanoengine, AMGA (anti-miRNA/GEM2-Azo), which significantly enhances the cytosolic delivery of anti-miRNA without requiring light irradiation, thereby facilitating precise targeting and synergistic chemo-gene therapy for triple-negative breast cancer (TNBC). AMGA can be rapidly internalized by cancer cells and specifically generate nanomechanical force to promote the efficient escape of anti-miRNAs from the endo/lysosome to the cytoplasm, simultaneously downregulating miR-21 and miR-10b. In comparison to Lipofectamine 2000, AMGA demonstrated superior efficacy in inhibiting the proliferation, migration, and invasion of cancer cells. Significantly, AMGA exhibited profound antitumor and gene silencing effects in an orthotopic human TNBC mouse model. This novel supramolecular nanoengine presents a promising strategy for cytosolic delivery of anti-miRNAs.

MicroRNAs (miRNAs) are a class of small non-coding RNAs that are associated with biochemical pathways through the post-transcriptional regulation of gene expression in different cell types. Based on their expression pattern and function, miRNAs can have oncogenic and tumor suppressor activities in different cancer cells. Altered mitochondrial function and bioenergetics are known hallmarks of cancer cells. Mitochondria play a central role in metabolic reprogramming during cancer progression. Cancer cells exploit mitochondrial function for cell proliferation, invasion, migration and metastasis. Genetic and epigenetic changes in nuclear genome contribute to altered mitochondrial function and metabolic reprogramming in cancer cells. Recent studies have identified the role of miRNAs as major facilitators of anterograde and retrograde signaling between the nucleus and mitochondria in cancer cells. Detailed analysis of the miRNA-mediated regulation of mitochondrial function in cancer cells may provide new avenues for the diagnosis, prognosis, and therapeutic management of the disease. Our review aims to discuss the role of miRNAs in nuclear-mitochondrial crosstalk regulating mitochondrial functions in different cancer types. We further discussed the potential application of mitochondrial miRNAs (mitomiRs) targeting mitochondrial biogenesis and metabolism in developing novel cancer therapy.

Diabetic kidney disease (DKD), a.k.a diabetic nephropathy, is a leading cause of end-stage renal disease. However, in a fair percentage of patients with type-2 diabetes, renal involvement also occurs due to non-diabetic reasons (non-diabetic kidney disease, NDKD). In this study, we identified miRNA-mRNA regulatory networks specific to human DKD pathogenesis. miRNA profiling of the renal biopsy from cases (DKD, n = 5), disease controls (T2DM with NDKD, n = 6), and non-diabetic, non-CKD controls (patients undergoing nephrectomy for renal cancer, n = 3) revealed 68 DKD-specific miRNA regulation. Sixteen target mRNAs of these DKD-miRNAs were found to have a negative association with the estimated glomerular filtration rate (eGFR) in patients with DKD. The renal gene expression and eGFR data of DKD patients (n = 10-18) in the NephroSeq database were used. Based on these findings, 11 miRNA-mRNA regulatory networks were constructed for human DKD pathogenesis. Of these, in-vitro validation of miR-192-5p- CDKN3 (Cell cycle-dependent kinase inhibitor 3) network was done as miR-192-5p exhibited a maximum number of target genes in the identified DKD regulatory networks, and CDKN3 appeared as a novel target of miR-192-5p in our study. We demonstrated that miR-192-5p overexpression or knockdown of CDKN3 attenuated high glucose-induced apoptosis, fibrotic gene expression, cell hypertrophy, and cell cycle dysregulation and improved viability of proximal tubular cells. Moreover, miR-192-5p overexpression significantly inhibited CDKN3 mRNA and protein expression in proximal tubular cells. Overall, 11 miRNA-mRNA regulatory networks were predicted for human DKD pathogenesis; among these, the association of miR-192-5p- CDKN3 network DKD pathogenesis was confirmed in proximal tubular cell culture.

Alopecia areata (AA) is an autoimmune disorder characterized by non-scarring hair loss. Despite the growing understanding of its immune-related pathogenesis, biomarkers for early diagnosis and disease severity assessment remain limited. Recent studies have suggested that microRNAs (miRNAs) play a crucial role in regulating immune responses and inflammation in autoimmune diseases. This study aimed to investigate the expression levels of three miRNAs, miR-19b-3p, miR-182-5p, and miR-155-5p, in AA patients and their potential as diagnostic markers and indicators of disease severity. A total of 67 AA patients and 62 healthy controls were included in this case-control study. The severity of AA was evaluated using the Severity of Alopecia Tool (SALT) score, categorizing patients into mild, moderate, and severe groups. Plasma miRNA extraction was performed using the Direct-zol™ RNA MiniPrep kit, and qRT-PCR analysis was conducted to quantify the expression levels of miR-19b-3p, miR-182-5p, and miR-155-5p. Diagnostic accuracy was assessed using Receiver Operating Characteristic (ROC) curve analysis, and correlation analysis was performed to examine the relationship between miRNA expression and disease severity. The results revealed that the expression of miR-19b-3p, miR-182-5p, and miR-155-5p was significantly higher in AA patients compared to healthy controls (p = 0.001 for all three miRNAs). ROC curve analysis demonstrated high diagnostic accuracy, with AUC values of 0.99 for miR-19b-3p, 0.95 for miR-182-5p, and 0.97 for miR-155-5p. These miRNAs showed high sensitivity and specificity, indicating their strong potential as diagnostic biomarkers. Moreover, correlation analysis revealed a significant association between miR-155-5p expression and the severity of AA (p < 0.001), suggesting its potential as a marker of disease progression. This study highlights the significant upregulation of miR-19b-3p, miR-182-5p, and miR-155-5p in AA patients, indicating their potential as minimally invasive diagnostic markers. Furthermore, the correlation between miRNA expression and disease severity provides valuable insights into the molecular mechanisms underlying AA. These findings suggest that miRNAs, particularly miR-155-5p, may serve as promising biomarkers for diagnosing and monitoring the progression of AA, potentially aiding in the development of targeted therapeutic strategies.

MicroRNAs (miRNAs) have emerged as crucial regulators in digestive pathologies, including inflammatory bowel disease (miR-31, miR-155, and miR-21), colorectal cancer (miR-21, miR-598, and miR-494), and non-alcoholic fatty liver disease (miR-21, miR-192, and miR-122). Their capacity to modulate gene expression at the post-transcriptional level makes them highly promising candidates for biomarkers and therapeutic interventions. However, despite considerable progress, their clinical application remains challenging. Research has shown that miRNA expression is highly dynamic, varying across patients, disease stages, and different intestinal regions. Their dual function as both oncogenes and tumor suppressors further complicates their therapeutic use, as targeting miRNAs may yield unpredictable effects. Additionally, while miRNA-based therapies hold great potential, significant hurdles persist, including off-target effects, immune activation, and inefficiencies in delivery methods. The intricate interplay between miRNAs and gut microbiota adds another layer of complexity, influencing disease mechanisms and treatment responses. This review examined the role of miRNAs in digestive pathologies, emphasizing their diagnostic and therapeutic potential. While they offer new avenues for disease management, unresolved challenges underscore the need for further research to refine their clinical application.

Loss-of-function mutations in the chromodomain helicase DNA-binding 8 (CHD8) gene are strongly associated with autism spectrum disorders (ASDs). Indeed, the reduction of CHD8 causes transcriptional, epigenetic, and cellular phenotypic changes correlated to disease, which can be monitored in assessing new therapeutic approaches. SINEUPs are a functional class of natural and synthetic antisense long non-coding RNAs able to stimulate the translation of sense target mRNA, with no effect on transcription. Here, we employed synthetic SINEUP-CHD8 targeting the first and third AUG of the CHD8 coding sequence to efficiently stimulate endogenous CHD8 protein production. SINEUP-CHD8 were effective in cells with reduced levels of the target protein and in patient-derived fibroblasts with CHD8 mutations. Functionally, SINEUP-CHD8 were able to revert molecular phenotypes associated with CHD8 suppression, i.e., genome-wide transcriptional dysregulation, and the reduction of H3K36me3 levels. Strikingly, in chd8-morpholino-treated and ENU mutant zebrafish embryos, SINEUP-chd8 injection confirmed the ability of SINEUP RNA to rescue the chd8-suppression-induced macrocephaly phenotype and neuronal hyperproliferation. Thus, SINEUP-CHD8 molecule(s) represent a proof-of-concept toward the development of an RNA-based therapy for neurodevelopmental syndromes with implications for, and beyond ASD, and relevant to genetic disorders caused by protein haploinsufficiency.

MicroRNA (miRNA)-based therapy holds significant potential; however, its structural limitations pose a challenge to the full exploitation of its biomedical functionality. Framework nucleic acids are promising owing to their transportability, biocompatibility, and functional editability. MiRNA-125 is embedded into a nucleic acid framework to create an enzyme-responsive nanoparachute (NP), enhancing the miRNA loading capacity while preserving the attributes of small-scale framework nucleic acids and circumventing the uncertainty related to RNA exposure in conventional loading methods. An enzyme-sensitive sequence is designed in NP as a bioswitchable apparatus for cargo miRNAs release. NP is compared with conventional delivery modes and delivery vehicles, confirming its excellent transportability and sustained release properties. Moreover, NP confers good enzyme and serum resistance to the cargo miRNAs. Simultaneously, it can easily deliver miRNA-125 to liver and kidney lesions owing to its passive targeting properties. This allows for Keap1/Nrf2 pathway regulation and p53 protein targeting in the affected tissues. Additionally, NP negatively regulates the expression of Bax and Caspase-3. These combined actions help to inhibit oxidation, prevent cell cycle arrest, and reduce the apoptosis of liver and kidney cells. Consequently, this strategy offers a potential treatment for acute liver and kidney injury.

Muscle regeneration is a vital biological process that is crucial for maintaining muscle function and integrity, particularly for the treatment of muscle diseases such as sarcopenia and muscular dystrophy. Generally, muscular tissues can self-repair and regenerate under various conditions, including acute or chronic injuries, aging, and genetic mutation. However, regeneration becomes challenging beyond a certain threshold, particularly in severe muscle injuries or progressive diseases. In recent years, liposome-based nanotechnologies have shown potential as promising therapeutic strategies for muscle regeneration. Liposomes offer an adaptable platform for targeted drug delivery due to their cell membrane-like structure and excellent biocompatibility. They can enhance drug solubility, stability, and targeted delivery while minimizing systemic side effects by different mechanisms. This review summarizes recent advancements, discusses current applications and mechanisms, and highlights challenges and future directions for possible clinical translation of liposome-based nanomaterials in the treatment of muscle diseases. It is hoped this review offers new insights into the development of liposome-enabled nanomedicine to address current limitations.

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

Immune function is highly controlled at the transcriptional level by the binding of transcription factors (TFs) to promoter and enhancer elements. Several TF families play major roles in immune gene expression, including NF-κB, STAT, IRF, AP-1, NRs, and NFAT, which trigger anti-pathogen responses, promote cell differentiation, and maintain immune system homeostasis. Aberrant expression, activation, or sequence of isoforms and variants of these TFs can result in autoimmune and inflammatory diseases as well as hematological and solid tumor cancers. For this reason, TFs have become attractive drug targets, even though most were previously deemed "undruggable" due to their lack of small molecule binding pockets and the presence of intrinsically disordered regions. However, several aspects of TF structure and function can be targeted for therapeutic intervention, such as ligand-binding domains, protein-protein interactions between TFs and with cofactors, TF-DNA binding, TF stability, upstream signaling pathways, and TF expression. In this review, we provide an overview of each of the important TF families, how they function in immunity, and some related diseases they are involved in. Additionally, we discuss the ways of targeting TFs with drugs along with recent research developments in these areas and their clinical applications, followed by the advantages and disadvantages of targeting TFs for the treatment of immune disorders.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease marked by abnormal B-cell proliferation and increased autoantibodies. miRNAs play a crucial role in regulating B-cell dysfunction and SLE pathology. miRNAs influence DNA methylation, B-cell activation, and gene expression, contributing to SLE pathogenesis. miRNAs impact B cells through key processes like proliferation, differentiation, tolerance, and apoptosis. miRNAs also exacerbate inflammation and immune responses by modulating Interleukin 4 (IL-4), IL-6, and interferon cytokines. Autophagy, a key degradation mechanism, is also regulated by specific miRNAs that impact SLE pathology. This article explores the role of multiple miRNAs in regulating B-cell development, proliferation, survival, and immune responses, influencing SLE pathogenesis. miRNAs like miR-23a, the miR-17 ∼ 92 family, and miR-125b/miR-221 affect B-cell development by regulating transcription factors, signaling pathways, and cell cycle genes. miRNAs such as miR-181a-5p and miR-23a-5p are differentially regulated across developmental stages, emphasizing their complex regulatory roles in B-cell biology. This article synthesizes miRNA-B cell interactions to offer new strategies and directions for SLE diagnosis and treatment.

The global prevalence of oral squamous cell carcinoma (OSCC) has been increasing. OSCC at the advanced stage tends to resist conventional treatment and causes local recurrence and distant metastasis, resulting in poor prognosis. Therefore, detecting this cancer at an early stage and performing early intervention are important. Promising biomarkers to detect OSCC have yet to be established; however, microRNAs (miRNAs/miRs) serve a crucial role in OSCC tumorigenesis and may be potential biomarkers. In the present case report, the availability of salivary miRNAs as a therapeutic and prognostic marker for patients with OSCC was assessed. The patient was a 33-year-old woman who was diagnosed with advanced OSCC of the tongue, and their miRNA profile isolated from a saliva sample at each clinical course was evaluated. Microarray analysis of the salivary samples revealed changes in the levels of four miRNAs (hsa-miR-6798-5p, miR-6803-5p, miR-6805-5p and miR-6845-5p) in accordance with the clinical course. Neoadjuvant chemotherapy and surgical procedure decreased the levels, whereas the levels increased when the patient was diagnosed with lung metastasis. Furthermore, tongue and lung metastatic lesion specimens exhibited expression of the vascular endothelial growth factor receptor-2, which is regulated by the four miRNAs. Accordingly, the present report proposed that salivary miRNAs could be a therapeutic and prognostic biomarker for OSCC.

Vascular smooth muscle cell (vSMC) dysfunction is a critical contributor to cardiovascular diseases, including atherosclerosis, restenosis and vein graft failure. Recent advances have unveiled a fascinating range of non-coding RNAs (ncRNAs) that play a pivotal role in regulating vSMC function. This review aims to provide an in-depth analysis of the mechanisms underlying vSMC dysfunction and the therapeutic potential of various ncRNAs in mitigating this dysfunction, either preventing or reversing it. We explore the intricate interplay of microRNAs, long-non-coding RNAs and circular RNAs, shedding light on their roles in regulating key signalling pathways associated with vSMC dysfunction. We also discuss the prospects and challenges associated with developing ncRNA-based therapies for this prevalent type of cardiovascular pathology. LINKED ARTICLES: This article is part of a themed issue Non-coding RNA Therapeutics. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v182.2/issuetoc.

Amphiphilic lipid oligonucleotide conjugates are powerful molecular-engineering materials that have been used for delivery of therapeutic oligonucleotides. However, conventional lipid oligonucleotide conjugates suffer from poor selectivity to target cells due to the nonspecific interaction between lipid tails and cell membranes. Herein, a reconfigurable DNA nanotweezer consisting of a c-Met aptamer and bischolesterol-modified antisense oligonucleotide was designed for c-Met-targeted delivery of therapeutic antisense oligonucleotides. The c-Met aptamer is used to keep the DNA nanotweezer in a "closed" state, which enables the hydrophobic interaction within bischolesterol moieties. As a result, the amphiphilic DNA nanotweezer shows only a weak interaction with the cell membrane. Upon the release of the c-Met aptamer, the DNA nanotweezer converts to an "open" state, which facilitates the insertion of a cholesterol moiety into the cell membrane. Thus, the reconfigurable DNA nanotweezer enables the selective membrane anchoring of the DNA nanotweezer in cancerous cells that highly expressed c-Met protein. Moreover, this amphiphilic DNA nanotweezer shows enhanced accumulation at the tumor site and the inhibition of tumor growth. Taking advantage of the stimuli-responsive membrane anchoring capability, this reconfigurable DNA nanotweezer could be further explored as a smart multifunctional platform for cancer therapy.

Prostate cancer (PCa) is a prevalent and lethal malignancy affecting males, with a considerable proportion of patients experiencing poor survival outcomes. The regulatory role of LIMD1-AS1 in the initiation and progression of PCa is emerging as a significant factor, however, the precise mechanisms governing its influence are yet to be fully elucidated.

qRT-PCR was employed to assess the expression of LIMD1-AS1 and miR-29c-3p. The Cell Counting Kit-8 (CCK-8) was used to assess cell proliferation in PCa cells. Apoptosis rates were determined using flow cytometry. Cell migration and invasion were evaluated using the transwell assay. The targeted relationship of LIMD1-AS1 and miR-29c-3p was confirmed through dual-luciferase reporter gene analysis.

Increased expression of LIMD1-AS1 and decreased expression of miR-29c-3p were observed in both tumor tissues and serum from PCa patients. LIMD1-AS1 exhibited diagnostic and prognostic significance in PCa patients. Functionally, LIMD1-AS1 modulated the expression of miR-29c-3p to potentiate the proliferative, migratory, and invasive capabilities of PCa cells while concurrently inhibiting apoptosis.

LncRNA LIMD1-AS1 promotes the advancement of PCa by regulating miR-29c-3p, indicating that LIMD1-AS1/miR-29c-3p axis could serve as potential therapeutic targets for the therapeutic intervention of PCa.

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract which affects millions of individuals worldwide. Despite advancements in treatment options, there is increasing interest in exploring natural interventions with minimal side effects. Cruciferous vegetables, such as broccoli, cabbage, and radishes, contain bioactive compounds known as glucosinolates (GLSs), which have shown promising effects in alleviating IBD symptoms. This review aims to provide a comprehensive overview of the physiological functions and mechanisms of cruciferous GLSs and their metabolites in the context of IBD. Reviewed studies demonstrated that GLSs attenuated all aspects of IBD, including regulating the intestinal microbiota composition, exerting antioxidant and anti-inflammatory effects, restoring intestinal barrier function, and regulating epigenetic mechanisms. In addition, a few interventions with GLS supplementation in clinical studies were also discussed. However, there are still several challenges and remaining knowledge gaps, including variations in animals' experimental outcomes, the bioavailability of certain compounds, and few clinical trials to validate their effectiveness in human subjects. Addressing these issues will contribute to a better understanding of the therapeutic potential of cruciferous GLSs and their metabolites in the management of IBD.

Transactivation Response Element RNA-binding Protein (TRBP2) is a double-stranded RNA-binding protein widely known for its critical contribution to RNA interference (RNAi), a conserved mechanism of gene-expression regulation mediated through small non-coding RNA moieties (ncRNAs). Nevertheless, TRBP2 has also proved to be involved in other molecular pathways and biological processes, such as cell growth, organism development, spermatogenesis, and stress response. Mutations or aberrant expression of TRBP2 have been previously associated with diverse human pathologies, including Alzheimer's disease, cardiomyopathy, and cancer, with TRBP2 playing an essential role(s) in proliferation, invasion, and metastasis of tumor cells.

Hence, the present study aims to investigate, via employment of advanced flow cytometry, immunofluorescence, cell transgenesis and bioinformatics technologies, new, still elusive, functions and properties of TRBP2, particularly regarding its cell cycle-specific control during cancer cell division.

We have identified a novel, mitosis-dependent regulation of TRBP2 protein expression, as clearly evidenced by the lack of its immunofluorescence-facilitated detection during mitotic phases, in several human cancer cell lines of different tissue origin. Notably, the obtained TRBP2-downregulation patterns seem to derive from molecular mechanisms that act independently of oncogenic activities (e.g., malignancy grade), metastatic capacities (e.g., low versus high), and mutational signatures (e.g., p53-/- or p53ΔΥ126) of cancer cells.

Taken together, we herein propose that TRBP2 serves as a novel cell cycle-dependent regulator, likely exerting mitosis-suppression functions, and, thus, its mitosis-specific downregulation can hold strong promise to be exploited for the efficient and successful prognosis, diagnosis, and (radio-/chemo-)therapy of diverse human malignancies, in the clinic.

Hepatocellular carcinoma (HCC) poses a significant global health challenge, necessitating innovative therapeutic strategies. MicroRNAs (miRNAs) have emerged as pivotal regulators of HCC pathogenesis, influencing key processes such as self-renewal, angiogenesis, glycolysis, autophagy, and metastasis. This article integrates findings from a comprehensive literature review and bioinformatics analysis to elucidate the role of miRNAs in HCC. We discuss how dysregulation of miRNAs can drive HCC initiation, progression, and metastasis by modulating various signaling pathways and target genes. Moreover, leveraging high-throughput technology and bioinformatics tools, we identify key miRNAs involved in multiple cancer hallmarks, offering insights into potential combinatorial therapeutic strategies. Through our analysis considering p-values and signaling pathways associated with key features, we unveil miRNAs with simultaneous roles across critical cancer characteristics, providing a basis for the development of high-performance biomarkers. The microRNAs, miR-34a-5p, miR-373-3p, miR-21-5p, miR-214-5p, miR-195-5p, miR-139-5p were identified to be shared microRNAs in stemness, angiogenesis, glycolysis, autophagy, EMT, and metastasis of HCC. However, challenges such as miRNA stability and delivery hinder the translation of miRNA-based therapeutics into clinical practice. This review underscores the importance of further research to overcome existing barriers and realize the full potential of miRNA-based interventions for HCC management.

Cancer is still a major challenge of human health. The abnormality of intracellular cancer-related signal pathways is an important mechanism for the occurrence of cancer.

We used a molecular-senor to act on the endogenous signal molecules within the cell to redirect the abnormal signal flows in the cell to treat cancer. Based on CRISPR-dCas12f procedures, we combined aptamers and ribozymes to construct riboswitches, which served as molecular switches to reprogram sgRNAs, so that CRISPR-dCas12f redirected the intracellular anti-cancer signal flows after sensing specific input signal molecules. In addition, the activated molecular sensors and the inhibitory molecular sensors were constructed by combining transcription factors (VP64) and transcription inhibitors (KRAB) to specifically activate and inhibit target genes of interest.

Our experimental results showed that the molecular sensors that we designed and constructed specifically sensed the endogenous signal molecules and then redirect the cancer related signal networks of cancer cells. In addition, corresponding logic gates were constructed to distinguish cancer cells from normal cells and redirect anticancer signal flows to trigger specific cancer immunotherapy.

The constructed molecular sensors constructed specifically recognized the signal molecules within the cell and redirected the endogenous signal pathway to reprogram the fate of cancer cells.

MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate gene expression by binding to target messenger RNA (mRNA) molecules and promoting their degradation or blocking their translation. Parkinson's disease (PD) is a neurodegenerative disorder caused by the loss of dopaminergic neurons in the substantia nigra. There is increasing evidence to suggest that miRNAs play a role in the pathogenesis of PD. Studies have identified several miRNAs that are dysregulated in the brains of PD patients, and animal models of the disease. MiRNA expression dysregulation contributes to the onset and progression of PD by modulating neuroinflammation, oxidative stress, and protein aggregation genes. Moreover, miRNAs have emerged as potential therapeutic targets for PD. This review elucidates the changes in miRNA expression profiles associated with PD, emphasising their potential as diagnostic biomarkers and therapeutic targets, and detailing specific miRNAs implicated in PD and their downstream targets. Integrated Insights into miRNA Function, Microglial Activation, Diagnostic, and Treatment Prospects in PD Note: This figure is an original figure created by the authors.

MicroRNAs (miRNAs), which are non-coding RNAs consisting of 18-24 nucleotides, play a crucial role in the regulatory pathways of inflammatory diseases. Several recent investigations have examined the potential role of miRNAs in forming Crohn's disease (CD). It has been suggested that miRNAs serve as diagnostics for both fibrosis and inflammation in CD due to their involvement in the mechanisms of CD aggravation and fibrogenesis. More information on CD pathophysiology could be obtained by identifying the miRNAs concerned with CD and their target genes. These findings have prompted several in vitro and in vivo investigations into the putative function of miRNAs in CD treatment. Although there are still many unanswered questions, the growing body of evidence has brought miRNA-based therapy one step closer to clinical practice. This extensive narrative study offers a concise summary of the most current advancements in CD. We go over what is known about the diagnostic and therapeutic benefits of miRNA mimicry and inhibition so far, and we see what additional miRNA family targets could be useful for treating CD-related inflammation and fibrosis.

Apelin, a bioactive peptide that serves as an endogenous ligand for the apelin receptor (APJ), is overexpressed in various types of cancers and contributes to cancer cell proliferation, viability, migration, angiogenesis, and metastasis, as well as immune deviation. Noncoding RNAs (ncRNAs) regulate gene expression, and there is growing evidence suggesting a bidirectional crosstalk between ncRNAs (including long noncoding RNAs [lncRNAs], circular RNAs [circRNAs], and microRNAs [miRNAs]) and apelin in cancers. Certain miRNAs can directly target the apelin and inhibit its expression, thereby suppressing tumor growth. It has been indicated that miR-224, miR-195/miR-195-5p, miR-204-5p, miR-631, miR-4286, miR-637, miR-4493, and miR-214-3p target apelin mRNA and influence its expression in prostate cancer, lung cancer, esophageal cancer, chondrosarcoma, melanoma, gastric cancer, glioma, and hepatocellular carcinoma (HCC), respectively. Moreover, circ-NOTCH1, circ-ZNF264, and lncRNA BACE1-AS upregulate apelin expression in gastric cancer, glioma, and HCC, respectively. On the other hand, apelin has been shown to regulate the expression of certain ncRNAs to affect tumorigenesis. It was revealed that apelin affects the expression of circ_0000004/miR-1303, miR-15a-5p, and miR-106a-5p in osteosarcoma, lung cancer, and prostate cancer, respectively. This review explains a bidirectional interplay between ncRNAs and apelin in cancers to provide insights concerning the molecular mechanisms underlying this crosstalk and potential implications for cancer therapy.

miR-155 is a class of cancer markers closely related to cancer metastasis and invasion. Combining in situ detection with gene silencing not only helps to analyze the information on the abundance and spatial location of microRNA expression in the cell but also synergizes the therapy. In this work, we prepared HD@CM vesicles with three hairpin DNAs by using MCF-7 cell membranes. The hairpin DNAs can be triggered by endogenous miR-155, which opens the autocatalytic molecular circuit (ACHA) and obtains Y-shaped DNA nanostructures. This nanostructure not only detects endogenous miR-155 with high sensitivity for in situ imaging but also enables gene regulation of intracellular survivin mRNA. The levels of miR-155 in MDA-MB-231, MCF-7, Hela, and HEK-293T cells are found to be 7703, 3978, 1696, and 1229 copies/cell, respectively, as detected by HD@CMs. The fluorescence produced by HD@CM after coincubation with different cells is found to be proportional to the intracellular miR-155 content by confocal imaging. In addition, the gene regulatory function of the Y-shaped DNA structure resulted in significant inhibition of survivin protein expression and apoptosis rates of up to 83%. We look forward to the future application of our HD@CM platform for the precise diagnosis and programmable treatment of clinical cancers.

Myelodysplastic syndromes (MDS) are a group of malignant clonal hematological disorders with heterogeneous clinical course and risk of transformation to acute myeloid leukemia. Genetic and epigenetic dysregulation, including alterations in microRNA (miRNA) expression, plays a pivotal role in MDS pathogenesis influencing disease development and progression. MiRNAs, known for their regulatory roles in gene expression, have emerged as promising biomarkers in various malignant diseases. This review aims to explore the diagnostic and prognostic roles of miRNAs in MDS. We discuss research efforts aimed at understanding the clinical utility of miRNAs in MDS management. MiRNA dysregulation is linked to specific chromosomal abnormalities in MDS, providing insights into the molecular landscape of the disease. Circulating miRNAs in plasma offer a less invasive avenue for diagnostic and prognostic assessment, with distinct miRNA profiles identified in MDS patients. Additionally, we discuss investigations concerning the role of miRNAs as markers for treatment response to hypomethylating and immunomodulating agents, which could lead to improved treatment decision-making and monitoring. Despite significant progress, further research in larger patient cohorts is needed to fully elucidate the role of miRNAs in MDS pathogenesis and refine personalized approaches to patient care.

Porcine circovirus type 2 (PCV2) infection leads to multi-system inflammation in pigs, and this effect can be achieved by upregulating host miR-21. The underlying mechanism of miR-21 regulates PCV2-induced inflammation is already known, however, how PCV2 regulates miR-21 levels and function using both autonomic and host factors remains to be further revealed. Here we present the first evidence that PCV2 ORF5 induces an inflammatory response by up-regulating miR-21 level through targeting nuclear miR-30d. In this study, we found that overexpression of ORF5 significantly increased miR-21 level and promoted the expression of inflammatory cytokines and activation of the NF-κB pathway, while ORF5 mutation had the opposite effect. Moreover, the differential expression of miR-21 could significantly change the pro-inflammatory effect of ORF5, indicating that ORF5 promotes inflammatory response by up-regulating miR-21. Bioinformatics analysis and clinical detection found that nuclear miR-30d was significantly down-regulated after ORF5 overexpression and PCV2 infection, and targeted pri-miR-21 and PCV2 ORF5. Functionally, we found that miR-30d inhibited the levels of miR-21 and inflammatory cytokines in cells. Mechanistically, we demonstrated that ORF5 inhibits miR-30d expression levels through direct binding but not via the circRNA pathway, and miR-30d inhibits miR-21 levels by targeting pri-miR-21. In summary, the present study revealed the molecular mechanism of ORF5 upregulation of miR-21, further refined the molecular chain of PCV2-induced inflammatory response and elucidated the role of miRNAs in it.

Neurodegenerative diseases that include Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), Huntington's disease (HD), and multiple sclerosis (MS) that arise due to numerous causes like protein accumulation and autoimmunity characterized by neurologic depletion which lead to incapacity in normal physiological function such as thinking and movement in these patients. Glial cells perform an important role in protective neuronal function; in the case of neuroinflammation, glial cell dysfunction can promote the development of neurodegenerative diseases. miRNA that participates in gene regulation and plays a vital role in many biological processes in the body; in the central nervous system (CNS), it can play an essential part in neural maturation and differentiation. In neurodegenerative diseases, miRNA dysregulation occurs, enhancing the development of these diseases. In this review, we discuss neurodegenerative disease (Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS)) and how miRNA is preserved as a diagnostic biomarker or therapeutic agent in these disorders. Finally, we highlight miRNA as therapy.

The occurrence of cancer is often closely related to multiple tumor markers, so it is important to develop multitarget detection methods. By the proper design of the input signals and logical operations of DNA logic gates, detection and diagnosis of cancer at different stages can be achieved. For example, in the early stages, specific input signals can be designed to correspond to early specific tumor markers, thereby achieving early cancer detection. In the late stage, logic gates for multitarget detection can be designed to simultaneously detect multiple biomarkers to improve diagnostic accuracy and comprehensiveness. In this work, we constructed a dual-target-triggered DNA logic gate for anchoring DNA tetrahedra, where methylene blue was embedded in the DNA tetrahedra to sensitize ZnO@CdS@Au, achieving ultrasensitive detection of the target substance. We tested the response of AND and OR logic gates to the platform. For AND logic gates, the sensing platform only responds when both miRNAs are present. In the concentration range of 10 aM to 10 nM, the photoelectric signal gradually increases with an increase of the target concentration. Subsequently, we used OR logic gates for miRNA detection. Even if only one target exists, the sensing platform exhibits excellent performance. Similarly, within the concentration range of 10 aM to 10 nM, the photoelectric signal gradually increases with an increase of the target concentration. The minimum detection limit is 1.10 aM. Whether it is the need to detect multiple targets simultaneously or only one of them, we can achieve it by selecting the appropriate logic gate. This strategy holds promising application prospects in fields such as biosensing, medical diagnosis, and environmental monitoring.

Our study employs pooled CRISPR screens, integrating 2D and 3D culture models, to identify miRNAs critical in Breast Cancer (BC) tumoursphere formation. These screens combine with RNA-seq experiments allowing identification of miRNA signatures and targets essential for tumoursphere growth. miR-4787-3p exhibits significant up-regulation in BC, particularly in basal-like BCs, suggesting its association with aggressive disease. Surprisingly, despite its location within the 5'UTR of a protein coding gene, which defines DROSHA-independent transcription start site (TSS)-miRNAs, we find it dependant on both DROSHA and DICER1 for maturation. Inhibition of miR-4787-3p hinders tumoursphere formation, highlighting its potential as a therapeutic target in BC. Our study proposes elevated miR-4787-3p expression as a potential prognostic biomarker for adverse outcomes in BC. We find that protein-coding genes positively selected in the CRISPR screens are enriched of miR-4787-3p targets. Of these targets, we select ARHGAP17, FOXO3A, and PDCD4 as known tumour suppressors in cancer and experimentally validate the interaction of miR-4787-3p with their 3'UTRs. Our work illuminates the molecular mechanisms underpinning miR-4787-3p's oncogenic role in BC. These findings advocate for clinical investigations targeting miR-4787-3p and underscore its prognostic significance, offering promising avenues for tailored therapeutic interventions and prognostic assessments in BC.

Abundant researches have consistently illustrated the crucial role of microRNAs (miRNAs) in a wide array of essential biological processes. Furthermore, miRNAs have been validated as promising therapeutic targets for addressing complex diseases. Given the costly and time-consuming nature of traditional biological experimental validation methods, it is imperative to develop computational methods. In the work, we developed a novel approach named efficient matrix completion (EMCMDA) for predicting miRNA-disease associations. First, we calculated the similarities across multiple sources for miRNA/disease pairs and combined this information to create a holistic miRNA/disease similarity measure. Second, we utilized this biological information to create a heterogeneous network and established a target matrix derived from this network. Lastly, we framed the miRNA-disease association prediction issue as a low-rank matrix-complete issue that was addressed via minimizing matrix truncated schatten p-norm. Notably, we improved the conventional singular value contraction algorithm through using a weighted singular value contraction technique. This technique dynamically adjusts the degree of contraction based on the significance of each singular value, ensuring that the physical meaning of these singular values is fully considered. We evaluated the performance of EMCMDA by applying two distinct cross-validation experiments on two diverse databases, and the outcomes were statistically significant. In addition, we executed comprehensive case studies on two prevalent human diseases, namely lung cancer and breast cancer. Following prediction and multiple validations, it was evident that EMCMDA proficiently forecasts previously undisclosed disease-related miRNAs. These results underscore the robustness and efficacy of EMCMDA in miRNA-disease association prediction.

Protein phosphatase 2A (PP2A), a heterotrimeric holoenzyme (scaffolding, catalytic, and regulatory subunits), regulates dephosphorylation for more than half of serine/threonine phosphosites and exhibits diverse cellular functions. Although several studies on natural products and miRNAs have emphasized their impacts on PP2A regulation, their connections lack systemic organization. Moreover, only part of the PP2A family has been investigated. This review focuses on the PP2A-modulating effects of natural products and miRNAs' interactions with potential PP2A targets in cancer and non-cancer cells. PP2A-modulating natural products and miRNAs were retrieved through a literature search. Utilizing the miRDB database, potential PP2A targets of these PP2A-modulating miRNAs for the whole set (17 members) of the PP2A family were retrieved. Finally, PP2A-modulating natural products and miRNAs were linked via a literature search. This review provides systemic directions for assessing natural products and miRNAs relating to the PP2A-modulating functions in cancer and disease treatments.