A decline in cellular quality control mechanisms is one of the processes of brain aging. Autophagy and proteostasis are two regulatory mechanisms that maintain cellular component turnover to preserve cellular homeostasis, optimal function, and neuronal health by eliminating damaged and aggregated proteins and preventing neurodegenerative disorders (NDDs). Impaired autophagy and proteostasis are significant hallmarks of aging and many age-related NDDs. MicroRNAs are noncoding RNA molecules that have recently been shown to be essential for regulating several biological processes, such as autophagy, proteostasis, cellular differentiation, and development by targeting mRNA's 3'untranslated region (3'UTR). During brain aging, miRNAs have been shown to dysregulate proteostasis and autophagy, resulting in abnormal cellular activity and protein aggregation, a characteristic of age-related NDDs. This review highlights the complex interactions of miRNAs in the orchestration of proteostasis and autophagy. This dysregulation impairs autophagic flux and proteostasis and accelerates age-related disorders, neuroinflammation, and neurodegeneration. Understanding the complex interactions among miRNAs, autophagy, and proteostasis in the aging brain is essential for novel therapeutics development for age-related NDDs.

Cardiovascular diseases (CVDs) are the leading causes of death worldwide, accounting for a significant burden on global health systems. The complexity of CVDs arises from their multifactorial etiology, including genetic, environmental, and lifestyle factors. Early diagnosis and effective treatment remain critical for reducing mortality and improving patient outcomes, yet conventional methods often fall short in providing precise, timely information for disease management. MicroRNAs are small non-coding RNAs that regulate gene expression and play pivotal roles in various biological processes, including cardiovascular health. Among them, miR-21 has garnered significant attention due to its involvement in cardiac remodeling, fibrosis, inflammation, and hypertrophy. Elevated levels of miR-21 are frequently observed in conditions such as myocardial infarction, heart failure, and coronary artery disease, positioning it as a potential biomarker for early detection and disease progression. Furthermore, therapeutic strategies targeting miR-21, such as antagomirs and innovative delivery systems, have shown promise in preclinical studies, though challenges like off-target effects and delivery inefficiencies persist. This review aims to provide a comprehensive understanding of miR-21's role in CVDs, addressing its potential as a diagnostic biomarker and therapeutic target. We discuss recent advancements, limitations, and future prospects in miR-21 research, emphasizing the importance of integrating this knowledge into clinical practice to improve CVD management.

This review highlights the role of miRNAs in various diseases affecting major organ systems. miRNAs are small, non-coding RNA molecules that regulate numerous genes. Dysregulation of miRNAs is linked to many pathological conditions due to their involvement in gene silencing and cellular pathways. We discuss miRNA expression patterns, their physiological and pathological roles, and how changes in miRNA levels contribute to disease. Notably, miRNAs like miR-499 and miR-21 are implicated in heart failure and atherosclerosis. miRNA dysregulation is also associated with colorectal and gastric cancers, influencing tumorigenesis and chemoresistance. In neurological diseases, miRNAs exhibit diverse profiles that affect neurodevelopment and degeneration. Additionally, miRNAs modulate cell function in reproductive organs, impacting fertility and cancer progression. miRNAs such as miR-192 and miR-204 serve as biomarkers for nephropathy and acute kidney injury. These miRNAs are involved in skeletal muscle diseases, contributing to conditions like osteoporosis and sarcopenia. miRNAs function as oncogenes or tumor suppressors in cancer, highlighting their potential in diagnostics and therapy. Further research is needed to develop miRNA-based diagnostics and treatments.

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.

Non-coding RNAs (ncRNAs) are composed of nucleotides that do not encode proteins but instead serve as guides. It interacts with amino acids at precise genomic sites, influencing chromatin structure and gene expression. These ncRNAs contribute to numerous inter-species dynamics, including those within the vector-host-pathogen triad. Vector-associated ncRNAs are released into hosts to combat the host immune system and sustain arthropod viability. Conversely, hosts may utilize specific ncRNAs as part of their defences to counteract pathogen-carrying vectors. Moreover, pathogens transmitted through vectors' saliva into hosts carry ncRNAs that enhances their virulence. While recent investigations have primarily focused on vector-associated ncRNAs in animal hosts, only a few have explored the functions of pathogen-associated ncRNAs and their role in initiating infections. Our review delves into the historical prospects of ncRNAs, mechanisms by which pathogen-derived ncRNAs influence host-pathogen interactions, regulate gene expression, and evade host defences. Ultimately, it underscores the importance ncRNAs mediated regulatory network in vector-host-pathogen dynamics, offering new strategies to combat vector-borne diseases and enhance public health outcomes.

Spinal cord injury (SCI) poses a substantial challenge in contemporary medicine, significantly impacting patients and society. Emerging research highlights a strong association between SCI and chronic pain, yet the molecular mechanisms remain poorly understood. To address this, we conducted bioinformatics and systems biology analyses to identify molecular biomarkers and pathways that link SCI to chronic pain. This study aims to elucidate these mechanisms and identify potential therapeutic targets.

Through analysis of the GSE151371 and GSE177034 databases, we identified differentially expressed genes (DEGs) linked to SCI and chronic pain. This analysis uncovered shared pathways, proteins, transcription factor networks, hub genes, and potential therapeutic drugs. Regression analysis on the hub genes facilitated the development of a prognostic risk model. Additionally, we conducted an in-depth examination of immune infiltration in SCI to elucidate its correlation with chronic pain.

Analyzing 101 DEGs associated with SCI and chronic pain, we constructed a protein interaction network and identified 15 hub genes. Using bioinformatics tools, we further identified 4 potential candidate genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed a strong correlation between SCI and chronic pain, particularly related to inflammation. Additionally, we examined the relationship between SCI and immune cell infiltration, discovering a significant link between SCI and T cell activation. This is notable as activated T cells can cause persistent inflammation and chronic pain. Lastly, we analyzed the hub genes to explore the transcription factor network, potential therapeutic drugs, and ceRNA networks.

The analysis of 15 hub genes as significant biological markers for SCI and chronic pain has led to the identification of several potential drugs for treatment.

The discovery of the involvement of microRNAs (miRNAs) in cystic fibrosis (CF) has generated increasing interest in the past years, due to their possible employment as a novel class of drugs to be studied in pre-clinical settings of therapeutic protocols for cystic fibrosis. In this narrative review article, consider and comparatively evaluate published laboratory information of possible interest for the development of miRNA-based therapeutic protocols for cystic fibrosis. We consider miRNAs involved in the upregulation of CFTR, miRNAs involved in the inhibition of inflammation and, finally, miRNAs exhibiting antibacterial activity. We suggest that antago-miRNAs and ago-miRNAs (miRNA mimics) can be proposed for possible validation of therapeutic protocols in pre-clinical settings.

Ferroptosis and immune responses are critical pathological events in spinal cord injury (SCI), whereas relative molecular and cellular mechanisms remain unclear.

Micro-array datasets (GSE45006, GSE69334), RNA sequencing (RNA-seq) dataset (GSE151371), spatial transcriptome datasets (GSE214349, GSE184369), and single cell RNA sequencing (scRNA-seq) datasets (GSE162610, GSE226286) were available from the Gene Expression Omnibus (GEO) database. Through weighted gene co-expression network analysis and differential expression analysis in GSE45006, we identified differentially expressed time- and immune-related genes (DETIRGs) associated with chronic SCI and differentially expressed ferroptosis- and immune-related genes (DEFIRGs), which were validated in GSE151371. Protein-protein interaction and microRNA-mRNA-transcription factor regulatory networks were constructed based on Search Tool for the Retrieval of Interacting Genes (STRING) and NetworkAnalyst, respectively, which were validated by chromatin immunoprecipitation followed by sequencing (ChIP-seq). Cell subclusters and unique features of microglia in SCI were identified by single-cell transcriptomic analysis, which were validated in GSE226286. Spatial expression patterns of DETIRGs and DEFIRGs were validated in brain injury (GSE214349) and SCI (GSE184369). Potential mechanisms underlying neuronal regeneration by neurotrophin-3 (NT3)-chitosan were revealed by transcriptomic analyses in GSE69334. Immune- and ferroptosis-related mechanisms of nanolayered double hydroxide loaded with NT3 (LDH-NT3) were investigated in vivo and in vitro.

GBP2, TEC, UNC93B1, PLXNC1, NFATC1, IL10RB, and TLR8 were DETIRGs represented chronic SCI-specific genes and peripheral blood biomarkers. NFKB1 may regulate expression of CYBB and HMOX1 in a unique subcluster of M1 microglia within the middle SCI lesion, establishing links between microglial ferroptosis and neuroinflammation. Reduced inflammatory responses and microglial ferroptosis were potential effects of NT3-chitosan or LDH-NT3 on neuronal regeneration.

A novel subcluster of microglia exhibiting M1 polarization and ferroptosis phenotype was involved in SCI. These microglia may trigger neuroinflammation and induce neuronal degeneration within the middle site of SCI, which might be inhibited by NT3-chitosan or LDH-NT3.

Argonautes (AGOs) are a type of protein that degrade specific messenger RNAs, consequently reducing the expression of a specific gene. These proteins consist of small, single-stranded RNA or DNA and may provide a route for detecting and silencing complementary mobile genetic elements. In this research, we investigated which AGO(s) were involved in Kawasaki disease (KD).

We obtained mRNA-level gene expression profiles from leukocyte samples that had previously been gathered in another study and uploaded to the NCBI GEO database. The Human Transcriptome Array (HTA 2.0) analysis included 50 children with KD prior to IVIG (KD1), 18 children with KD three weeks post-IVIG (KD3), 18 non-febrile controls (HC), and 18 febrile controls (FC), which were arranged in the quoted publications for all materials and methods in order to collect data. We used the default value of the commercialized microarray tool Partek to perform an analysis of variance and determine any significant fold changes (KD1, KD3, HC, and FC individually).

The data revealed that the AGO2 and AGO4 genes displayed significant within-group differences with p = 0.034 and 0.007, respectively. In AGO2, significant differences were observed between KD1 vs. HC + FC with p = 0.034. KD1 appears higher than the other specimens in AGO4, with significant differences between KD1 and HC (p = 0.033), KD1 and FC (p = 0.033), KD1 and KD3 (p = 0.013), and KD1 and HC + FC (p = 0.007). We observed no substantial differences in AGO1 or AGO3 (p > 0.05). There were no significant differences between AGO(s) and coronary artery lesions or intravenous immunoglobulin resistance. (p > 0.05) Conclusion: Endothelial cell inflammation and injury, two basic pathological mechanisms, are thought to be involved in coronary endothelial dysfunction in KD. AGO2 and AGO4 are likely to participate in the endothelial dysfunction of children with KD, with AGO4 potentially playing a key role, while AGO1 and AGO3 appear not to participate.

Pulmonary Hypertension (PH) is a complex cardiovascular disorder characterized by elevated blood pressure in the pulmonary arteries. Current therapeutic approaches for PH have limitations in addressing the underlying molecular mechanisms. This article explores the potential of noncoding RNAs (ncRNAs), including microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs), delivered through Lipid-Based Nanoparticles (LNPs) as a novel treatment strategy. These ncRNAs play critical roles in regulating vascular function and are implicated in PH pathogenesis. LNPs provide a promising method for the efficient and targeted delivery of ncRNAs. Advances in LNP technology, including the incorporation of R8 peptide modification, have shown promise in enhancing the delivery and efficacy of ncRNAs in PH models. Challenges such as biocompatibility, toxicity, and precise targeting must be addressed as these therapies move toward clinical application. The potential of personalized medicine and the integration of artificial intelligence in LNP design are discussed as prospects. In conclusion, ncRNA lipotherapeutics delivered via LNPs offer a transformative approach to treating PH, potentially leading to more effective management and improved patient outcomes in the future. However, continued research and clinical trials are necessary to fully realize their therapeutic potential in the field of PH treatment.

Ovarian cancer, a prevalent and deadly cancer among women, presents a significant challenge for early detection due to its heterogeneous nature. MicroRNAs, short non-coding regulatory RNA fragments, play a role in various cellular processes. Aberrant expression of these microRNAs has been observed in the carcinogenesis-related processes of many cancer types. Numerous studies highlight the critical role of microRNAs in the initiation and progression of ovarian cancer. Given their clinical importance and predictive value, there has been considerable interest in developing simple, prompt, and sensitive miRNA biosensor strategies. Among these, electrochemical sensors have demonstrated advantageous characteristics such as simplicity, sensitivity, low cost, and scalability. These microRNA-based electrochemical biosensors are valuable tools for early detection and point-of-care applications. This article discusses the potential role of microRNAs in ovarian cancer and recent advances in the development of electrochemical biosensors for miRNA detection in ovarian cancer samples.

Preeclampsia (PE) is a pregnancy-related syndrome that can lead to a variety of pathophysiological processes, such as impaired implantation. The pathogenesis of PE involves circular RNA (circRNA). The study aims to determine the role of a novel circRNA, circ_0003314, in trophoblast cell phenotypes. Circ_0003314, microRNA-26b-5p (miR-26b-5p) and IL-1 receptor accessory protein (IL1RAP) expression were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation was investigated by MTT assay and 5-Ethynyl-2'-deoxyuridine assay. Cell migration and invasion were investigated by transwell assay. Cell apoptotic rate and angiogenesis were investigated by flow cytometry analysis and tube formation assay, respectively. Protein expression was detected by western blotting. The binding relationship between miR-26b-5p and circ_0003314 or IL1RAP was identified using dual-luciferase reporter assay and RNA pull-down assay. Circ_0003314 and IL1RAP expression were significantly increased, while miR-26b-5p was decreased in placental tissues of PE patients. Circ_0003314 overexpression inhibited trophoblast cell proliferation, migration, invasion and angiogenesis and induced cell apoptosis. Additionally, circ_0003314 acted as a sponge for miR-26b-5p, and miR-26b-5p bound to IL1RAP. Introduction of miR-26b-5p or silencing of IL1RAP attenuated the effects of circ_0003314 overexpression on trophoblast cell phenotypes. Further, circ_0003314 induced IL1RAP expression through miR-26b-5p in trophoblast cells. Circ_0003314 regulated trophoblast cell phenotypes by increasing IL1RAP expression through binding to miR-26b-5p.

The endoplasmic reticulum (ER) is an important organelle in eukaryotic cells, responsible for a range of biological functions such as the secretion, modification and folding of proteins, maintaining Ca2+ homeostasis and the synthesis of steroids/lipids, secreted proteins and membrane proteins. When cells are affected by internal or external factors, including abnormal energy metabolism, disrupted Ca2+ balance, altered glycosylation, drug toxicity, and so on, the unfolded or misfolded proteins accumulate in the ER, leading to the unfolded protein response (UPR) and ER stress. The abnormal ER stress has been reported to be involved in various pathological processes. MicroRNAs (miRNAs) are non-coding RNAs with the length of approximately 19-25 nucleotides. They control the expression of multiple genes through posttranscriptional gene silencing in eukaryotes or some viruses. Increasing evidence indicates that miRNAs are involved in various cellular functions and biological processes, such as cell proliferation and differentiation, growth and development, and metabolic homeostasis. Hence, miRNAs participate in multiple pathological processes. Recently, many studies have shown that miRNAs play an important role by regulating ER stress in ischemia-reperfusion (I/R) injury, but the relevant mechanisms are not fully understood. In this review, we reviewed the current understanding of ER stress, as well as the biogenesis and function of miRNAs, and focused on the role of miRNAs regulation of ER stress in I/R injury, with the aim of providing new targets for the treatment of I/R injury.

In the innate immune system, the cyclic GMP-AMP synthase (cGAS)-interferon gene stimulator (STING) pathway activates the type I interferon (IFN) response and the NF-κB pathway by recognizing double-stranded DNAs, the imbalance of which plays a pivotal role in human diseases, including cancer, autoimmune and inflammatory diseases. Non-coding RNAs (ncRNAs) are a diverse group of transcripts that do not code for proteins but regulate various targets and signaling pathways in physiological and pathological processes. Recently, there has been increasing interest in investigating the interplay between the cGAS-STING pathway and ncRNAs. In this review, we provide a concise overview of the cGAS-STING pathway and ncRNAs. Then, we specifically delve into the regulation of the cGAS-STING pathway by long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs), the three major classes of ncRNAs, and the influence of the cGAS-STING pathway on the expression of ncRNAs. Furthermore, we introduce the therapeutic applications targeting the cGAS-STING pathway and ncRNA therapy, and propose the utilization of drug delivery systems to deliver ncRNAs that influence the cGAS-STING pathway. Overall, this review highlights the emerging understanding of the intricate relationship between the cGAS-STING pathway and ncRNAs, shedding light on their potential as therapeutic targets in various diseases.

Vascular neogenesis, an early event in the development of rheumatoid arthritis (RA) inflammation, is critical for the formation of synovial vascular networks and plays a key role in the progression and persistence of chronic RA inflammation. microRNAs (miRNAs), a class of single-stranded, non-coding RNAs with approximately 21-23 nucleotides in length, regulate gene expression by binding to the 3' untranslated region (3'-UTR) of specific mRNAs. Increasing evidence suggests that miRNAs are differently expressed in diseases associated with vascular neogenesis and play a crucial role in disease-related vascular neogenesis. However, current studies are not sufficient and further experimental studies are needed to validate and establish the relationship between miRNAs and diseases associated with vascular neogenesis, and to determine the specific role of miRNAs in vascular development pathways. To better treat vascular neogenesis in diseases such as RA, we need additional studies on the role of miRNAs and their target genes in vascular development, and to provide more strategic references. In addition, future studies can use modern biotechnological methods such as proteomics and transcriptomics to investigate the expression and regulatory mechanisms of miRNAs, providing a more comprehensive and in-depth research basis for the treatment of related diseases such as RA.

Ythdf2 is known to mediate mRNA degradation in an m6A-dependent manner, and it has been shown to play a role in skeletal muscle differentiation. Recently, Ythdf2 was also found to bind to m6A-modified precursor miRNAs and regulate their maturation. However, it remains unknown whether this mechanism is related to the regulation of myogenesis by Ythdf2. Here, we observed that Ythdf2 knockdown significantly suppressed myotube formation and impacted miRNAs expression during myogenic differentiation. Through integrated analysis of miRNA and mRNA sequencing data, miR-378 and miR-378-5p were identified as important targets of Ythdf2 in myogenesis. Mechanically, Ythdf2 was found to interact with core components of the pre-miRNA processor complex, namely DICER1 and TARBP2, thereby facilitating the maturation of pre-miR-378/miR-378-5p in an m6A-dependent manner and resulting in an increase in the expression levels of mature miR-378 and miR-378-5p. Moreover, the downregulation of either miR-378 or miR-378-5p significantly inhibited myotube formation, while the forced expression of miR-378 or miR-378-5p could partially rescued Ythdf2 knockdown-induced suppression of myogenic differentiation by activating the mTOR pathway. Collectively, our results for the first time suggest that Ythdf2 regulates myogenic differentiation via mediating pre-miR-378/miR-378-5p maturation, which might provide new insights into the molecular mechanisms underlying m6A modification in the regulation of myogenesis.

Previous studies have indicated that ψ-modified small RNAs play crucial roles in tumor metastasis. However, the ψ-modified small RNAs during metastasis of PTC are still unclear.

We compared the pseudouridine synthase 7 (PUS7) alteration between metastatic and non-metastatic PTCs, and investigated its correlation with clinicopathological features. Additionally, we employed a small RNA ψ modification microarray to examine the small RNA ψ modification profile in both metastatic and non-metastatic PTCs, as well as paired paracancerous tissues. The key molecule involved in ψ modification, pre-miR-8082, was identified and found to regulate the expression of CD47. Experiments in vitro were conducted to further investigate the function of PUS7 and CD47 in PTC.

Our results demonstrated that PUS7 was down-regulated in PTC and was closely associated with metastasis. Moreover, the ψ modification of pre-miR-8082 was found to be decreased, resulting in down-expression of pre-miR-8082 and miR-8082, leading to the loss of the inhibitory effect on CD47, thereby promoting tumor migration.

Our study demonstrates that PUS7 promotes the inhibition of CD47 and inhibits metastasis of PTC cells by regulating the ψ modification of pre-miR-8082. These results suggest that PUS7 and ψ pre-miR-8082 may serve as potential targets and diagnostic markers for PTC metastasis.

Cancer-associated fibroblasts are the most important cellular component of the tumor microenvironment, controlling cancer progression and therapeutic response. These cells in the tumor microenvironment regulate tumor progression and development as oncogenic or tumor suppressor agents. However, the mechanisms by which CAFs communicate with cancer cells remain to investigate. Here, we review evidence that extracellular vesicles, particularly exosomes, serve as vehicles for the intercellular transfer of bioactive cargos, notably microRNAs and long non-coding RNAs, from CAFs to cancer cells. We try to highlight molecular pathways of non-coding RNAs and the interaction among these molecules. Together, these findings elucidate a critical exosome-based communication axis by which CAFs create mostly a supportive pro-tumorigenic microenvironment and highlight therapeutic opportunities for disrupting this intercellular crosstalk.

Background/Objectives: Patients with endometriosis still respond poorly to progestins due to progesterone resistance associated with microRNAs (miRNAs). The aim of this study was to investigate the expression of selected miRNAs, estrogen receptor (ER)α, ERβ, progesterone receptor (PR)-A and PR-B and to determine the target genes of upregulated miRNAs in endometriosis. Methods: In this study, 18 controls, 18 eutopic and 18 ectopic samples were analysed. Profiling and validation of miRNAs associated with functions of endometriosis were performed using next-generation sequencing (NGS) and qRT-PCR. At the same time, the expression of ERα, ERβ, PR-A and PR-B was also determined using qRT-PCR. Target prediction was also performed for miR-199a-3p, miR-1-3p and miR-125b-5p using StarBase. Results: In this study, NGS identified seven significantly differentially expressed miRNAs, of which six miRNAs related to the role of endometriosis were selected for validation by qRT-PCR. The expression of miR-199a-3p, miR-1-3p, miR-146a-5p and miR-125b-5p was upregulated in the ectopic group compared to the eutopic group. Meanwhile, ERα and ERβ were significantly differentially expressed in endometriosis compared to the control group. However, the expressions of PR-A and PR-B showed no significant differences between the groups. The predicted target genes for miR-199a-3p, miR-1-3p and miR-125b-5p are SCD, TAOK1, DDIT4, LASP1, CDK6, TAGLN2, G6PD and ELOVL6. Conclusions: Our findings demonstrated that the expressions of ERα and ERβ might be regulated by miRNAs contributing to progesterone resistance, whereas the binding of miRNAs to target genes could also contribute to the pathogenesis of endometriosis. Therefore, miRNAs could be used as potential biomarkers and for targeted therapy in patients with endometriosis.

Bone health is ensured by the coordinated action of two types of cells-the osteoblasts that build up bone structure and the osteoclasts that resorb the bone. The loss of balance in their action results in pathological conditions such as osteoporosis. Central to this study is a class of RNA-binding proteins (RBPs) that regulates the biogenesis of miRNAs. In turn, miRNAs represent a critical level of regulation of gene expression and thus control multiple cellular and biological processes. The impact of miRNAs on the pathobiology of various multifactorial diseases, including osteoporosis, has been demonstrated. However, the role of RBPs in bone remodeling is yet to be elucidated. The aim of this study is to dissect the transcriptional landscape of genes encoding the compendium of 180 RBPs in bone cells. We developed and applied a multi-modular integrative analysis algorithm. The core methodology is gene expression analysis using the GENEVESTIGATOR platform, which is a database and analysis tool for manually curated and publicly available transcriptomic data sets, and gene network reconstruction using the Ingenuity Pathway Analysis platform. In this work, comparative insights into gene expression patterns of RBPs in osteoblasts and osteoclasts were obtained, resulting in the identification of 24 differentially expressed genes. Furthermore, the regulation patterns upon different treatment conditions revealed 20 genes as being significantly up- or down-regulated. Next, novel gene-gene associations were dissected and gene networks were reconstructed. Additively, a set of osteoblast- and osteoclast-specific gene signatures were identified. The consolidation of data and information gained from each individual analytical module allowed nominating novel promising candidate genes encoding RBPs in osteoblasts and osteoclasts and will significantly enhance the understanding of potential regulatory mechanisms directing intracellular processes in the course of (patho)physiological bone turnover.

The aetiology of CL/P is complicated, with both genetic and environmental factors. This study aimed to investigate the association between TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) exposure and changes in the expression of miR-214-3p in the context of cleft palate.

In this study, we established a fetal mouse cleft palate model using TCDD and differentially expressed miRNAs were analysed by microarray analysis and verified by qRT-PCR. Finally, we demonstrated the effects of TCDD and microRNAs on the proliferation and migration of mesenchymal cells by using CCK8, EDU, Transwell, and wound-healing assays.

Our findings revealed significant upregulation of miRNAs such as miR-214-3p, miR-296-5p, and miR-33-5p in the TCDD intervention group, while miRNAs like miR-92a-3p, miR-126a-3p, and miR-411-5p were significantly downregulated. Notably, qRT-PCR testing confirmed a significant difference in miR-214-3P expression. Further investigations involved the overexpression of miR-214-3p, reducing cell proliferation and migration in primary mouse embryonic palatal mesenchymal (MEPM) cells.

These results are consistent with the finding that TCDD suppresses palatal mesenchymal cell proliferation and migration through miR-214-3p. In conclusion, miR-214-3p probably plays a role in TCDD-induced cleft palates in mice.

Lenvatinib (LEN) is a multi-target TKI, which plays a pivotal role in the treatment of advanced hepatocellular carcinoma (HCC). The inevitable occurrence of drug resistance still prevents curative potential and is deleterious for the prognosis, and a growing body of studies is accumulating, which have devoted themselves to unveiling its underlying resistance mechanism and made some progress. The dysregulation of crucial signaling pathways, non-coding RNA and RNA modifications were proven to be associated with LEN resistance. A range of drugs were found to influence LEN therapeutic efficacy. In addition, the superiority of LEN combination therapy has been shown to potentially overcome the limitations of LEN monotherapy in a series of research, and a range of promising indicators for predicting treatment response and prognosis have been discovered in recent years. In this review, we summarize the latest developments in LEN resistance, the efficacy and safety of LEN combination therapy as well as associated indicators, which may provide new insight into its resistance as well as ideas in the treatment of advanced HCC.

Type 2 diabetes mellitus (T2DM) is a metabolic disease that is characterized by chronic hyperglycaemia. MicroRNAs (miRNAs) are single-stranded, small non-coding RNAs that play important roles in post-transcriptional gene regulation. They are negative regulators of their target messenger RNAs (mRNAs), in which they bind either to inhibit mRNA translation, or to induce mRNA decay. Similar to proteins, miRNAs exist in different isoforms (isomiRs). miRNAs and isomiRs are selectively loaded into small extracellular vesicles, such as the exosomes, to protect them from RNase degradation. In T2DM, exosomal miRNAs produced by different cell types are transported among the primary sites of insulin action. These interorgan crosstalk regulate various T2DM-associated pathways such as adipocyte inflammation, insulin signalling, and β cells dysfunction among many others. In this review, we first focus on the mechanism of exosome biogenesis, followed by miRNA biogenesis and isomiR formation. Next, we discuss the roles of exosomal miRNAs and isomiRs in the development of T2DM and provide evidence from clinical studies to support their potential roles as T2DM biomarkers. Lastly, we highlight the use of exosomal miRNAs and isomiRs in personalized medicine, as well as addressing the current challenges and future opportunities in this field. This review summarizes how research on exosomal miRNAs and isomiRs has developed from the very basic to clinical applications, with the goal of advancing towards the era of personalized medicine.

The low abundance, heterogeneous expression, and temporal changes of miRNA in different cellular locations pose significant challenges for both the detection sensitivity of miRNA liquid biopsy and intracellular imaging. In this work, we report an intelligently assembled biosensor based on catalytic hairpin assembly (CHA) and aggregation-induced emission (AIE), named as catalytic hairpin aggregation-induced emission (CHAIE), for the ultrasensitive detection and intracellular imaging of miRNA-155. To achieve such goal, tetraphenylethylene-N3 (TPE-N3) is used as AIE luminogen (AIEgen), while graphene oxide is introduced to quench the fluorescence. When the target miRNA is present, CHA reaction is triggered, causing the AIEgen to self-assemble with the hairpin DNA. This will restrict the intramolecular rotation of the AIEgen and produce a strong AIE fluorescence. Interestingly, CHAIE does not require any enzyme or expensive thermal cycling equipment, and therefore provides a rapid detection. Under optimal conditions, the proposed biosensor can determine miRNA in the concentration range from 2 pM to 200 nM within 30 min, with the detection limit of 0.42 pM. The proposed CHAIE biosensor in this work offers a low background signal and high sensitivity, making it applicable for highly precise spatiotemporal imaging of target miRNA in living cells.

MicroRNAs (miRNAs) are small non-coding RNAs comprising 19-24 nucleotides that indirectly control gene expression. In contrast to other non-coding RNAs (ncRNAs), circular RNAs (circRNAs) are defined by their covalently closed loops, forming covalent bonds between the 3' and 5' ends. circRNAs regulate gene expression by interacting with miRNAs at transcriptional or post-transcriptional levels. Accordingly, circRNAs and miRNAs control many biological events related to cancer, including cell proliferation, metabolism, cell cycle, and apoptosis. Both circRNAs and miRNAs are involved in the pathogenesis of diseases, such as breast cancer. This review focuses on the latest discoveries on dysregulated circRNAs and miRNAs related to breast cancer, highlighting their potential as biomarkers for clinical diagnosis, prognosis, and chemotherapy response.

Gene regulation is crucial for cellular function and homeostasis. It involves diverse mechanisms controlling the production of specific gene products and contributing to tissue-specific variations in gene expression. The dysregulation of genes leads to disease, emphasizing the need to understand these mechanisms. Computational methods have jointly studied transcription factors (TFs), microRNA (miRNA), and messenger RNA (mRNA) to investigate gene regulatory networks. However, there remains a knowledge gap in comprehending gene regulatory networks. On the other hand, super-enhancers (SEs) have been implicated in miRNA biogenesis and function in recent experimental studies, in addition to their pivotal roles in cell identity and disease progression. However, statistical/computational methodologies harnessing the potential of SEs in deciphering gene regulation networks remain notably absent. However, to understand the effect of miRNA on mRNA, existing statistical/computational methods could be updated, or novel methods could be developed by accounting for SEs in the model. In this review, we categorize existing computational methods that utilize TF and miRNA data to understand gene regulatory networks into three broad areas and explore the challenges of integrating enhancers/SEs. The three areas include unraveling indirect regulatory networks, identifying network motifs, and enriching pathway identification by dissecting gene regulators. We hypothesize that addressing these challenges will enhance our understanding of gene regulation, aiding in the identification of therapeutic targets and disease biomarkers. We believe that constructing statistical/computational models that dissect the role of SEs in predicting the effect of miRNA on gene regulation is crucial for tackling these challenges.

Tuberculosis (TB) is a global threat, affecting one-quarter of the world's population. The World Health Organization (WHO) reports that 6 million people die annually due to chronic illnesses, a statistic that includes TB-related deaths. This high mortality is attributed to factors such as the emergence of drug-resistant strains and the exceptional survival mechanisms of Mycobacterium tuberculosis (MTB). Recently, microRNAs (miRNAs) have garnered attention for their crucial role in TB pathogenesis, surpassing typical small RNAs (sRNA) in their ability to alter the host's immune response. For instance, miR-155, miR-125b, and miR-29a have been identified as key players in the immune response to MTB, particularly in modulating macrophages, T cells, and cytokine production. While sRNAs are restricted to within cells, exo-miRNAs are secreted from MTB-infected macrophages. These exo-miRNAs modify the function of surrounding cells to favor the bacterium, perpetuating the infection cycle. Another significant aspect is that the expression of these miRNAs affects specific genes and pathways involved in immune functions, suggesting their potential use in diagnosing TB and as therapeutic targets. This review compiles existing information on the immunomodulatory function of exosomal miRNAs from MTB, particularly focusing on disease progression and the scientific potential of this approach compared to existing diagnostic techniques. Thus, the aim of the study is to understand the role of exosomal miRNAs in TB and to explore their potential for developing novel diagnostic and therapeutic methods.

Exosome-miR-146a is significantly increased in patients with Atherosclerosis (AS), but its mechanism and effect on AS have not been fully elucidated.

To explore the change rule and mechanism of exosomes release, and the role and molecular mechanism of exosome-miR-146a in AS.

We isolated and identified exosomes from THP-1 macrophages after treating them with ox-LDL. Then used co-immunoprecipitation and silver staining to identify the proteins involved in regulating exosome release. PKH67 was used to label exosomes to confirm that cells can absorb them, and then co-culture with HVSMCs for cell proliferation and migration detection. The target genes of miR-146a were screened and identified through bioinformatics and luciferase activity assay, and the expression of miR-146a and related proteins was detected through qRT-PCR and Western blot in HUVECs. An AS model in LDLR-/- mice induced by a high-fat diet was developed to investigate the impact of exosome-miR-146a on AS.

The results showed that experimental foam cells from AS showed higher expression of miR-146a. It was observed that NMMHC IIA and HSP70 interacted to regulate the release of exosomes. And HUVECs can absorb exosomes derived from macrophages. In addition, we also found that miR-146a directly targeted the SMAD4 gene to modulate the p38 MAPK signaling pathway, thereby mediating HUVECs damage. Furthermore, exosome-miR-146a induced abnormal proliferation and migration of HVSMCs. The expression of miR-146a was significantly reduced in miR-146a-mimics mice and increased in miR-146a inhibitor mice whereas the inhibition of miR-146a effectively reduced while increasing miR-146a worsened AS in mice.

Our findings expressed the potential of miR-146a as a favorable therapeutic target for AS, however, further exploration is suggestive for deep understanding of the mechanisms regulating exosome-miR-146a release in vivo and to develop effective therapeutic strategies involving miR-146a.

Preeclampsia (PE) is a pregnancy complication associated with multi-organ damage and vascular dysfunction. Meanwhile, microRNAs or miRNAs are crucial regulators of gene expression in various diseases including PE. Our previous studies reported high expression of miR-510 in the PE patients' blood compared to normal. Hence, we hypothesize that miR-510-3p targets Vascular endothelial growth factor A (VEGFA) in the regulation of PI3K/AKT/eNOS/mTOR axis in PE and miR-510-3p could be a potential therapeutic target for PE.

The proliferation, migration, and apoptosis of HTR8/SVNeo and BeWo cells were analyzed by manipulating the miR-510-3p and VEGFA expression. Similarly, the inhibition of miR-510-3p through anti-miR-510-3p was analyzed in PE rat models, and the biochemical, hemodynamic parameters, and histopathology were examined between the groups. Moreover, the expression of miR-510-3p and VEGFA/PI3K/AKT/eNOS/mTOR axis was analyzed using qRT-PCR and Western blot.

Significant changes were observed in the BP, proteinuria, and other biochemical parameters between PE and control rats. Our results suggest that miR-510-3p targets VEGFA leading to vascular dysfunction in PE, while treatment with anti-miR-510-3p in the PE-induced rat model exhibits a significant change in the expression of miR-510-3p/VEGFA/PI3K/AKT/eNOS/mTOR signaling where miR-510-3p showed lesser expression and vice versa with VEGFA. The gene and protein expression analysis revealed a significant correlation between miR-510-3p and the VEGFA signaling axis in PE.

Thus, our findings from in vitro and in vivo suggest miR-510-3p as a potential therapeutic target and anti-miR-510-3p as a novel therapeutic molecule for PE.

The dysfunction of several types of regulators, including miRNAs, has recently attracted scientific attention for their role in cancer-associated changes in gene expression. MiRNAs are small RNAs of ~22 nt in length that do not encode protein information but play an important role in post-transcriptional mRNA regulation. Studies have shown that miRNAs are involved in tumour progression, including cell proliferation, cell cycle, apoptosis, and tumour angiogenesis and invasion, and play a complex and important role in the regulation of tumourigenesis. The detection of selected miRNAs may help in the early detection of cancer cells, and monitoring changes in their expression profile may serve as a prognostic factor in the course of the disease or its treatment. MiRNAs may serve as diagnostic and prognostic biomarkers, as well as potential therapeutic targets for colorectal cancer. In recent years, there has been increasing evidence for an epigenetic interaction between DNA methylation and miRNA expression in tumours. This article provides an overview of selected miRNAs, which are more frequently expressed in colorectal cancer cells, suggesting an oncogenic nature.

Frontonasal malformations are caused by a failure in the growth of the frontonasal prominence during development. Although genetic studies have identified genes that are crucial for frontonasal development, it remains largely unknown how these genes are regulated during this process. Here, we show that microRNAs, which are short non-coding RNAs capable of targeting their target mRNAs for degradation or silencing their expression, play a crucial role in the regulation of genes related to frontonasal development in mice. Using the Mouse Genome Informatics (MGI) database, we curated a total of 25 mouse genes related to frontonasal malformations, including frontonasal hypoplasia, frontonasal dysplasia, and hypotelorism. MicroRNAs regulating the expression of these genes were predicted through bioinformatic analysis. We then experimentally evaluated the top three candidate miRNAs (miR-338-5p, miR-653-5p, and miR-374c-5p) for their effect on cell proliferation and target gene regulation in O9-1 cells, a neural crest cell line. Overexpression of these miRNAs significantly inhibited cell proliferation, and the genes related to frontonasal malformations (Alx1, Lrp2, and Sirt1 for miR-338-5p; Alx1, Cdc42, Sirt1, and Zic2 for miR-374c-5p; and Fgfr2, Pgap1, Rdh10, Sirt1, and Zic2 for miR-653-5p) were directly regulated by these miRNAs in a dose-dependent manner. Taken together, our results highlight miR-338-5p, miR-653-5p, and miR-374c-5p as pathogenic miRNAs related to the development of frontonasal malformations.

Dysregulation of miRNAs is closely related to the progression of various diseases, so identifying disease-related miRNAs is crucial. Most recently proposed methods are based on graph reasoning, while they did not completely exploit the topological structure composed of the higher-order neighbor nodes and the global and local features of miRNA and disease nodes. We proposed a prediction method, MDAP, to learn semantic features of miRNA and disease nodes based on various meta-paths, as well as node features from the entire heterogeneous network perspective, and node pair attributes. Firstly, for both the miRNA and disease nodes, node category-wise meta-paths were constructed to integrate the similarity and association connection relationships. Each target node has its specific neighbor nodes for each meta-path, and the neighbors of longer meta-paths constitute its higher-order neighbor topological structure. Secondly, we constructed a meta-path specific graph convolutional network module to integrate the features of higher-order neighbors and their topology, and then learned the semantic representations of nodes. Thirdly, for the entire miRNA-disease heterogeneous network, a global-aware graph convolutional autoencoder was built to learn the network-view feature representations of nodes. We also designed semantic-level and representation-level attentions to obtain informative semantic features and node representations. Finally, the strategy based on the parallel convolutional-deconvolutional neural networks were designed to enhance the local feature learning for a pair of miRNA and disease nodes. The experiment results showed that MDAP outperformed other state-of-the-art methods, and the ablation experiments demonstrated the effectiveness of MDAP's major innovations. MDAP's ability in discovering potential disease-related miRNAs was further analyzed by the case studies over three diseases.

The use of nanomaterials in gene editing and synthetic biology has emerged as a pivotal strategy in the pursuit of refined treatment methodologies for pulmonary disorders. This review discusses the utilization of nanomaterial-assisted gene editing tools and synthetic biology techniques to promote the development of more precise and efficient treatments for pulmonary diseases. First, we briefly outline the characterization of the respiratory system and succinctly describe the principal applications of diverse nanomaterials in lung ailment treatment. Second, we elaborate on gene-editing tools, their configurations, and assorted delivery methods, while delving into the present state of nanomaterial-facilitated gene-editing interventions for a spectrum of pulmonary diseases. Subsequently, we briefly expound on synthetic biology and its deployment in biomedicine, focusing on research advances in the diagnosis and treatment of pulmonary conditions against the backdrop of the coronavirus disease 2019 pandemic. Finally, we summarize the extant lacunae in current research and delineate prospects for advancement in this domain. This holistic approach augments the development of pioneering solutions in lung disease treatment, thereby endowing patients with more efficacious and personalized therapeutic alternatives.

Spinal cord injury (SCI) can cause loss of sensory and motor function below the level of injury, posing a serious threat to human health and quality of life. One significant characteristic feature of pathological changes following injury in the nervous system is demyelination, which partially contributes to the long-term deficits in neural function after injury. The remyelination in the central nervous system (CNS) is mainly mediated by oligodendrocyte progenitor cells (OPCs). Numerous complex intracellular signaling and transcriptional factors regulate the differentiation process from OPCs to mature oligodendrocytes (OLs) and myelination. Studies have shown the importance of microRNA (miRNA) in regulating OPC functions. In this review, we focus on the demyelination and remyelination after SCI, and summarize the progress of miRNAs on OPC functions and remyelination, which might provide a potential therapeutic target for SCI treatments.

Targeting specific organs and cell types using nanotechnology and sophisticated delivery methods has been at the forefront of applicative biomedical sciences lately. Macrophages are an appealing target for immunomodulation by nanodelivery as they are heavily involved in various aspects of many diseases and are highly plastic in their nature. Their continuum of functional "polarization" states has been a research focus for many years yielding a profound understanding of various aspects of these cells. The ability of monocyte-derived macrophages to metamorphose from pro-inflammatory to reparative and consequently to pro-resolving effectors has raised significant interest in its therapeutic potential. Here, we briefly survey macrophages' ontogeny and various polarization phenotypes, highlighting their function in the inflammation-resolution shift. We review their inducing mediators, signaling pathways, and biological programs with emphasis on the nucleic acid sensing-IFN-I axis. We also portray the polarization spectrum of macrophages and the characteristics of their transition between different subtypes. Finally, we highlighted different current drug delivery methods for targeting macrophages with emphasis on nanotargeting that might lead to breakthroughs in the treatment of wound healing, bone regeneration, autoimmune, and fibrotic diseases.

Senescence-associated microRNAs (SA-miRNAs) are important molecules for aging regulation. While many aging-promoting SA-miRNAs have been identified, confirmed aging-suppressive SA-miRNAs are rare, that impeded our full understanding on aging regulation. In this study, we verified that miR-708 expression is decreased in senescent cells and aged tissues and revealed that miR-708 overexpression can alleviate cellular senescence and aging performance. About the molecular cascade carrying the aging suppressive action of miR-708, we unraveled that miR-708 directly targets the 3'UTR of the disabled 2 (Dab2) gene and inhibits the expression of DAB2. Interestingly, miR-708-caused DAB2 downregulation blocks the aberrant mammalian target of rapamycin complex 1 (mTORC1) activation, a driving metabolic event for senescence progression, and restores the impaired autophagy, a downstream event of aberrant mTORC1 activation. We also found that AMP-activated protein kinase (AMPK) activation can upregulate miR-708 via the elevation of DICER expression, and miR-708 inhibitor is able to blunt the antiaging effect of AMPK. In summary, this study characterized miR-708 as an aging-suppressive SA-miRNA for the first time and uncovered a new signaling cascade, in which miR-708 links the DAB2/mTOR axis and AMPK/DICER axis together. These findings not only demonstrate the potential role of miR-708 in aging regulation, but also expand the signaling network connecting AMPK and mTORC1.

microRNAs (miRNAs) are a class of non-coding, small RNAs that play an important role in diverse biological processes and diseases. By regulating the expression of eukaryotic genes post-transcriptionally in a sequence-specific manner, miRNAs are widely used to design synthetic RNA switches. However, most of the RNA switches are often dependent on the corresponding ligand molecules, whose specificity and concentration would affect the efficiency of synthetic RNA circuits. Here, a fused transcriptional repressor Gal4BD-Rluc based gene-switch system Gal-miR for miRNA visualization and gene regulation is described. By placing a luciferase downstream gene under the control of endogenous miRNA machinery, the Gal-miR system makes the conversion of miRNA-mediated gene silencing into a ratiometric bioluminescent signal, which quantitatively reflected miRNA-206 activity during myogenic differentiation. Moreover, it demonstrates that this gene-switch system can effectively inhibit breast cancer cell viability, migration and invasion under the control of specific miRNAs by replacing the downstream gene with melittin functional gene. The study proposes a powerful modular genetic design for achieving precise control of transgene expression in a miRNA responsive way, as well as visualizing the dynamics of miRNA activity.

AI-enabled synthetic biology has tremendous potential but also significantly increases biorisks and brings about a new set of dual use concerns. The picture is complicated given the vast innovations envisioned to emerge by combining emerging technologies, as AI-enabled synthetic biology potentially scales up bioengineering into industrial biomanufacturing. However, the literature review indicates that goals such as maintaining a reasonable scope for innovation, or more ambitiously to foster a huge bioeconomy do not necessarily contrast with biosafety, but need to go hand in hand. This paper presents a literature review of the issues and describes emerging frameworks for policy and practice that transverse the options of command-and-control, stewardship, bottom-up, and laissez-faire governance. How to achieve early warning systems that enable prevention and mitigation of future AI-enabled biohazards from the lab, from deliberate misuse, or from the public realm, will constantly need to evolve, and adaptive, interactive approaches should emerge. Although biorisk is subject to an established governance regime, and scientists generally adhere to biosafety protocols, even experimental, but legitimate use by scientists could lead to unexpected developments. Recent advances in chatbots enabled by generative AI have revived fears that advanced biological insight can more easily get into the hands of malignant individuals or organizations. Given these sets of issues, society needs to rethink how AI-enabled synthetic biology should be governed. The suggested way to visualize the challenge at hand is whack-a-mole governance, although the emerging solutions are perhaps not so different either.

MicroRNAs (miRNAs) are 19-23 nucleotide long, evolutionarily conserved noncoding RNA molecules that regulate gene expression at the post-transcriptional level. In this review, involvement of miRNAs is summarized in the differentiation and function of immune cells, in anti-infective immune responses, immunodeficiencies and autoimmune diseases. Roles of miRNAs in anticancer immunity and in the transplantation of solid organs and hematopoietic stem cells are also discussed. Major focus is put on the translational clinical applications of miRNAs, including the establishment of noninvasive biomarkers for differential diagnosis and prediction of prognosis. Patient selection and response prediction to biological therapy is one of the most promising fields of application. Replacement or inhibition of miRNAs has enormous therapeutic potential, with constantly expanding possibilities. Although important challenges still await solutions, evaluation of miRNA fingerprints may contribute to an increasingly personalized management of immune dysregulation with a remarkable reduction in toxicity and treatment side effects. More detailed knowledge of the molecular effects of physical exercise and nutrition on the immune system may facilitate self-tailored lifestyle recommendations and advances in prevention.

Ksp1 is a casein II-like kinase whose activity prevents aberrant macroautophagy/autophagy induction in nutrient-rich conditions in yeast. Here, we describe a kinase-independent role of Ksp1 as a novel autophagic receptor protein for Ssn2/Med13, a known cargo of Snx4-assisted autophagy of transcription factors. In this pathway, a subset of conserved transcriptional regulators, Ssn2/Med13, Rim15, and Msn2, are selectively targeted for vacuolar proteolysis following nitrogen starvation, assisted by the sorting nexin heterodimer Snx4-Atg20. Here we show that phagophores also engulf Ksp1 alongside its cargo for vacuolar proteolysis. Ksp1 directly associates with Atg8 following nitrogen starvation at the interface of an Atg8-family interacting motif (AIM)/LC3-interacting region (LIR) in Ksp1 and the LIR/AIM docking site (LDS) in Atg8. Mutating the LDS site prevents the autophagic degradation of Ksp1. However, deletion of the C terminal canonical AIM still permitted Ssn2/Med13 proteolysis, suggesting that additional non-canonical AIMs may mediate the Ksp1-Atg8 interaction. Ksp1 is recruited to the perivacuolar phagophore assembly site by Atg29, a member of the trimeric scaffold complex. This interaction is independent of Atg8 and Snx4, suggesting that Ksp1 is recruited early to phagophores, with Snx4 delivering Ssn2/Med13 thereafter. Finally, normal cell survival following prolonged nitrogen starvation requires Ksp1. Together, these studies define a kinase-independent role for Ksp1 as an autophagic receptor protein mediating Ssn2/Med13 degradation. They also suggest that phagophores built by the trimeric scaffold complex are capable of receptor-mediated autophagy. These results demonstrate the dual functionality of Ksp1, whose kinase activity prevents autophagy while it plays a scaffolding role supporting autophagic degradation.Abbreviations: 3-AT: 3-aminotriazole; 17C: Atg17-Atg31-Atg29 trimeric scaffold complex; AIM: Atg8-family interacting motif; ATG: autophagy related; CKM: CDK8 kinase module; Cvt: cytoplasm-to-vacuole targeting; IDR: intrinsically disordered region; LIR: LC3-interacting region; LDS: LIR/AIM docking site; MoRF: molecular recognition feature; NPC: nuclear pore complex; PAS: phagophore assembly site; PKA: protein kinase A; RBP: RNA-binding protein; UPS: ubiquitin-proteasome system. SAA-TF: Snx4-assisted autophagy of transcription factors; Y2H: yeast two-hybrid.

Circulating miRNAs (cirmiRNAs) can be packaged into the exosomes, participating in intercellular communication, which affects the malignant progression and therapy resistance of triple-negative breast cancer (TNBC). Currently, immune checkpoint inhibitors that regulate T-cell function, especially antibodies against programmed cell death 1 (PD-1) or its ligand PD-L1, are emerging as new promising therapy for TNBC patients. However, only very limited patients showed complete or partial response to anti-PD-1 treatment. Dysfunction of CD8+ T cells is one of the key reasons for the immune escape of TNBC. The regulation of exosome-derived cirmiRNAs on CD8+ T cells in TNBC deserves more investigation. Here, the cirmiR-20a-5p level was significantly upregulated in the plasma of TNBC patients and culture supernatant of TNBC cells. High abundance of cirmiR-20a-5p was correlated with a worse prognosis of TNBC. cirmiR-20a-5p was secreted in the form of exosomes by TNBC cells. Exosomal cirmiR-20a-5p was internalized into CD8+ T cells and resulted into the dysfunction of CD8+ T. A mechanism study uncovered that cirmiR-20a-5p targeted the nuclear protein ataxia-telangiectasia (NPAT) and decreased NPAT expression in CD8+ T cells. An in vivo xenograft mouse model showed that cirmiR-20a-5p conferred TNBC to anti-PD-1 treatment resistance. Collectively, these findings indicated that cirmiR-20a-5p released by TNBC cells via exosome promotes cancer cell growth and leads to the immunosuppression by inducing CD8+ T cell dysfunction. This study suggests that targeting cirmiR-20a-5p might be a novel strategy for overcoming the resistance of TNBC to anti-PD-1 immunotherapy.

miRNAs play a crucial therapeutic role in diseases such as cancer, diabetes and viral infections, with around 1900 identified in the human genome. Some have progressed to clinical trials, and miRNA mimics and miRNA inhibitors are pivotal therapeutic molecules undergoing evaluation. The review delves into various miRNA-associated clinical trials, emphasizing their precision in targeting specific genes, modulating disease pathways and diagnostic potential. This underscores the importance of miRNA therapy, foreseeing innovations in precision medicine techniques for diverse diseases. The future envisions improved delivery systems addressing challenges like immunogenicity and digestion, while a comprehensive miRNA-based omics database could guide the development of tailored antisense miRNAs, further advancing precision medicine strategies.

Hirschsprung's disease (HSCR) is a rare developmental disorder in which enteric ganglia are missing along a portion of the intestine. HSCR has a complex inheritance, with RET as the major disease-causing gene. However, the pathogenesis of HSCR is still not completely understood. Therefore, we applied a computational approach based on multi-omics network characterization and clustering analysis for HSCR-related gene/miRNA identification and biomarker discovery. Protein-protein interaction (PPI) and miRNA-target interaction (MTI) networks were analyzed by DPClusO and BiClusO, respectively, and finally, the biomarker potential of miRNAs was computationally screened by miRNA-BD. In this study, a total of 55 significant gene-disease modules were identified, allowing us to propose 178 new HSCR candidate genes and two biological pathways. Moreover, we identified 12 key miRNAs with biomarker potential among 137 predicted HSCR-associated miRNAs. Functional analysis of new candidates showed that enrichment terms related to gene ontology (GO) and pathways were associated with HSCR. In conclusion, this approach has allowed us to decipher new clues of the etiopathogenesis of HSCR, although molecular experiments are further needed for clinical validations.

In recent years, a very close relationship between miRNA and cardiovascular diseases has been found. RAH and T2DM are accompanied by a change in the microRNA expression spectrum.

This study aimed to evaluate the clinical characteristics and expression of selected microRNAs in patients with idiopathic RAH and T2DM.

A total of 115 patients with RAH were included in this study. Among them were 53 patients (46.09%) with T2DM. miRNA levels were determined using quantitative real-time polymerase chain reaction. The expression of the examined genes was calculated from the formula RQ = 2-ΔΔCT.

Analysis using the Mann-Whitney U test showed a statistically significant (p < 0.05) difference in the expression of MIR1-1 (p = 0.031) and MIR195 (p = 0.042) associated with the occurrence of T2DM in the subjects. The value of MIR1-1 gene expression was statistically significantly higher in patients with T2DM (median: 0.352; mean: 0.386; standard deviation: 0.923) compared to patients without T2DM (median: 0.147; mean: -0.02; standard deviation: 0.824). The value of MIR195 gene expression was statistically significantly higher in patients with T2DM (median: 0.389, mean: 0.442; standard deviation: 0.819) compared to patients without T2DM (median: -0.027; mean: 0.08; standard deviation: 0.942).

The values of MIR1-1 and MIR195 gene expression were statistically significantly higher in patients with RAH and T2DM compared to patients with RAH and without T2DM. Further studies are necessary to precisely clarify the roles of miRNAs in patients with RAH and T2DM. They should demonstrate the utility of these genetic markers in clinical practice.

MicroRNAs (miRNAs) play crucial roles in skin pigmentation in animals. Rainbow trout (Oncorhynchus mykiss) is a key economic fish species worldwide, and skin color directly affects its economic value. However, the functions of miRNAs in rainbow trout skin pigmentation remain largely unknown. Herein, we overexpressed and silenced miR-495 in vitro and in vivo to investigate its functions. The analysis of spatial and temporal expression patterns suggested that miR-495 is a potential regulator during the process of skin pigmentation. In vitro, mc1r was validated as a direct target for miR-495 by dual-luciferase reporter assay, and overexpression of miR-495 significantly inhibited mc1r expression; in contrast, mc1r and its downstream gene mitf levels were markedly upregulated by decreased miR-495. In vivo, overexpressed miR-495 by injecting agomiR-495 led to a substantial decrease in the expression of mc1r and mitf in dorsal skin and liver, while the opposite results were obtained after miR-495 silencing by antagomiR-495. These findings suggested that miR-495 can target mc1r to regulate rainbow trout skin pigmentation, which provide a potential basis for using miRNAs as target drugs to treat pigmentation disorders and melanoma.