Search Results (1,069)

The fungus Penicillium digitatum causes citrus green mold, a major postharvest disease. Understanding the molecular mechanisms underlying its development is crucial for devising effective control strategies. In this study, we performed a comprehensive transcriptomic analysis of P. digitatum across three key developmental stages: spores, germinated spores, and mycelia. A total of 2175 novel mRNAs, 3957 novel long non-coding RNAs (lncRNAs), and 144 circular RNAs (circRNAs) were identified in P. digitatum. Genetic variation analysis revealed 12,396 Insertion-Ddeletion and 23,264 single nucleotide polymorphisms, with their prevalence decreasing as development progressed. The expression levels, temporal expression patterns and significant differences in mRNAs and lncRNAs across different developmental stages were also observed. Functional enrichment analysis of differentially expressed mRNAs and differentially expressed lncRNA target genes highlighted key biological processes and pathways associated with macromolecular metabolism, signal transduction, DNA replication, and reactive oxygen species scavenging. Additionally, differential expression analysis explored the potential interactions between differentially expressed lncRNAs and their target genes, as well as those between lncRNAs and circRNAs. Our findings provide valuable insights into the complex regulatory networks underpinning the development and pathogenicity of P. digitatum, offering a foundation for future research aimed at controlling green mold. Full article

Mesenchymal stromal/stem cells (MSCs) appear in many studies, and their utilization is a developing area of study. Scientists are investigating the abilities of MSCs and the possibilities of using them in anticancer therapies, as well as combining such therapies with those currently used clinically. This article provides an overview of MSC-based therapeutic strategies, assessing their potential in the context of cancer treatment. These are engineering or biotechnological approaches that utilize the natural properties of MSCs in a targeted and therapeutically effective manner. The review focuses on innovative methods such as genetic modifications to express desired therapeutic molecules, highlighting their potential applications in clinical practice. Innovative strategies include modifications to express anticancer proteins, miRNA (microRNA), siRNA (small interfering RNA), lncRNA (long non-coding RNA), and circRNA (circular RNA) that induce specific effects, as well as the delivery of therapeutic genes and oncolytic viruses. However, further studies are required to address the existing impediments, which are also discussed in this review. A major challenge in the clinical application of MSCs is their bidirectional role, an issue that remains a central focus of current research and is examined in this article. Full article

Background: Milk fat metabolism is a complex process regulated by non-coding RNAs. circRNAs (circRNAs) can act as miRNA sponges to regulate target gene expression. Purpose: This study aimed to investigate the role and mechanism of the circRNA_01754/miR-302c/LATS2 axis in regulating milk fat metabolism in bovine mammary epithelial cells (BMECs). Methods: mRNA sequencing was performed on bovine mammary gland tissues from different lactation stages to analyze the expression profiles. The interactions between circRNA_01754, miR-302c, and LATS2 were verified using dual-luciferase reporter assays, qRT-PCR, and Western blot. The functional effects on triglyceride (TAG) and cholesterol synthesis were assessed. Results: CircRNA_01754 was identified as a direct sponge for miR-302c. Overexpression of circRNA_01754 increased LATS2 expression by sequestering miR-302c. Functional experiments showed that circRNA_01754 and LATS2 promoted TAG synthesis, whereas miR-302c inhibited it. Furthermore, miR-302c was found to regulate the expression of YAP1, a key effector of the Hippo pathway, through LATS2. Conclusions: Our findings reveal that circRNA_01754 promotes milk fat synthesis by acting as a ceRNA for miR-302c to upregulate LATS2. This study lays the groundwork for producing high-quality milk and opens up new avenues for enhancing public dietary health. Full article

Hepatitis C virus (HCV) infection remains a major global health challenge and often progresses to chronic liver disease and hepatocellular carcinoma (HCC). Growing evidence indicates that epigenetic regulation mediated by non-coding RNAs plays a critical role in viral pathogenesis and tumor development. This review provides an integrated overview of the functions of microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) in HCV-induced liver injury. We highlight the dual roles of these molecules, demonstrating how some ncRNAs promote viral replication, whereas others act as tumor suppressors that become dysregulated during infection. Particular emphasis is placed on interaction networks in which lncRNAs and circRNAs function as molecular sponges for miRNAs, thereby modulating signaling pathways essential for hepatic homeostasis. Disruption of these networks contributes to a pro-inflammatory and pro-tumorigenic microenvironment. Finally, we discuss the potential of these transcripts as diagnostic biomarkers and as emerging therapeutic targets in HCV-associated HCC. Full article

Circular RNAs (circRNAs) emerge as alternate regulators of gene expression. CircRNAs are generated by back-splicing processes, are highly conserved, and are resistant to degradation. Recent advances in sequencing and computational tools have led to the discovery of the critical regulatory roles of these molecules in different physiological and pathological processes. Different functions of circRNAs in many physiological processes have been reported in the past few years, such as miRNA sponge activity, protein decoy/sponge/recruiter activity, deviation from parental gene expression, and encoding proteins/peptides. Additionally, circRNAs are being used clinically as biomarkers. Technological advances in molecular biology over the past few years have led to the development of various techniques for detecting, quantifying, manipulating, and analyzing the functions of circRNAs. This article summarizes different wet lab techniques for preparing, detecting, validating, localizing, and interacting with circRNAs, as well as determining miRNA sponge activity and functional analysis. Full article

Preeclampsia (PE) is an obstetric disorder with significant risks to both maternal and fetal health, characterized by hypertension and multi-organ dysfunction. Central to its pathogenesis is the impaired differentiation and function of trophoblast cells, leading to abnormal placental development and defective uterine vascular remodeling. This dysfunctional placentation triggers a cascade of oxidative stress, systemic inflammation, and immune dysregulation, collectively exacerbating disease severity. The trophoblast regulates maternal–fetal interactions through complex and tightly controlled gene expression networks, in which non-coding RNAs such as microRNAs (miRNAs) and circular RNAs (circRNAs) play essential regulatory roles. Here, we summarize current findings on transcriptomic alterations associated with trophoblast anomalies in PE and discuss their potential translational applications. Understanding these molecular mechanisms may enhance early diagnosis, improve clinical outcomes, and pave the way for precision medicine and individualized therapeutic strategies in PE. Full article

Glioblastoma (GBM), the most common primary malignant brain tumor in adults, has a median survival of 14–15 months despite aggressive treatment. Monitoring relies on MRI, but differentiating tumor progression from pseudo-progression or radiation necrosis remains difficult. Plasma extracellular vesicles (EVs) are emerging as promising non-invasive biomarkers due to their molecular cargos and accessibility. This review evaluates studies that specifically isolated plasma EVs for molecular profiling in GBM diagnosis and monitoring. Biomarkers (miRNA, RNA, DNA, proteins), EV characterization methods, and advancements in enriching tumor-derived EV subpopulations and assessing their diagnostic and prognostic potential are highlighted. Plasma EVs carry diverse cargos, including miRNAs (e.g., miR-21, miR-15b-3p), mRNAs (e.g., EGFRvIII), circRNAs, and proteins (e.g., CD44, GFAP). Composite molecular signatures have achieved sensitivities of 87–100% and specificities of 73–100% for GBM diagnosis. Tumor-derived EVs, enriched using techniques like SEC-CD44 immunoprecipitation, microfluidic platforms, or 5-ALA-induced PpIX fluorescence, enhance biomarker detection. Non-tumor-derived EVs may also reflect GBM’s systemic effects. Challenges include EV heterogeneity, non-EV contamination, and variable biomarker expression across studies. Plasma-EV-based liquid biopsies offer significant potential for GBM monitoring, with advanced enrichment methods improving tumor-specific biomarker detection. Standardizing isolation protocols and validating biomarkers in larger cohorts are critical for clinical translation. Full article

(1) Background: Swine hepatitis E (SHE) is a novel zoonotic disease caused by the swine hepatitis E virus. Open Reading Frame 3 (ORF3) is an important virulence protein of swine hepatitis E virus, which promotes the survival and replication of the virus within host cells by regulating the ERK pathway, modulating the transport of growth factors that affect apoptosis, and facilitating the transmission of death signals during HEV infection. (2) Methods: In our previous study, we used adenovirus-mediated overexpression of HEV-4 in swine ORF3 in HepG2 cells, extracted total RNA, and performed high-throughput lncRNA, circRNA, and transcriptome sequencing. Based on the role of ORF3 in regulating the innate immunity of host cells, maintaining ERK activity, inhibiting the transport of growth factors, and suppressing the immune response, the pathways and differentially expressed genes were screened. A clustering analysis was conducted on circRNAs and lncRNAs, which were significantly differentially expressed across the four pathways, and a regulatory network of circRNA-miRNA and lncRNA-mRNA was constructed. (3) Results: In this study, a total of 24 circRNAs and 4 lncRNAs were screened in HepG2 cells expressing ORF3 of HEV-4 in swine, including 8 circRNAs that regulate host cell innate immunity and 18 circRNAs that maintain ERK activity. Four circRNAs inhibited growth factor transport, and three circRNAs inhibited immune responses, predicting the regulatory networks of circRNA-miRNA and lncRNA-mRNA, respectively. (4) Conclusions: In this study, differential genes involved in regulating host cell innate immunity, maintaining ERK activity, inhibiting growth factor transport, and inhibiting immune response processes were successfully screened in HepG2 cells expressing ORF3 in HEV-4 in swine, and the regulatory networks of circRNA-miRNA and lncRNA-mRNA were predicted, respectively, which laid a foundation for further elucidating the function of swine hepatitis E virus ORF3 and elucidating the infection mechanism of swine hepatitis E virus. Full article

(1) Background: After HBV infection, viral transcripts and host RNA form a multi-layered interwoven regulatory network. However, a comprehensive map encompassing mRNA, miRNA, lncRNA, and circRNA is still lacking. This absence complicates the systematic explanation of the molecular mechanisms driving immune escape and metabolic reprogramming during the persistent infection stage. (2) Methods: In this study, we established a mouse model of chronic HBV infection and analyzed the differential expression of mRNA, miRNA, lncRNA, and circRNA through whole transcriptome sequencing (WTS). We constructed a competing endogenous RNA (ceRNA) network to systematically evaluate the overall impact of HBV on the host’s immune-metabolic pathways. (3) Results: RNA sequencing results indicated that HBV infection significantly up-regulated 194 mRNAs, 18 miRNAs, 184 lncRNAs, and 28 circRNAs, while down-regulating 42, 16, 122, and 31 corresponding transcripts, respectively. The differentially expressed genes were primarily enriched in pathways related to metabolism, immunity/inflammation, and signal transduction-ligand receptor interactions. Furthermore, the competitive endogenous RNA networks of lncRNA-miRNA-mRNA and circRNA-miRNA-mRNA constructed on this basis further identified miR-185-3p as a key core node. (4) Conclusions: In this study, based on whole transcriptome data, the gene expression profiles of rcccDNA/Ad-infected Alb-Cre transgenic mice (chronic HBV infection model) and normal Alb-Cre mice were systematically compared, and the core regulatory factor miR-185-3p of key differentially expressed genes was screened. The microRNA is expected to provide a new target for the precise treatment of chronic hepatitis B by targeted intervention of viral replication and high liver inflammation. Full article

Breast cancer remains the leading cause of cancer-related death in women worldwide. This disease is characterized by its molecular and phenotypic heterogeneity, which hinders the development of effective therapies. While two-dimensional (2D) monolayer cell cultures are widely used, they are insufficient to reproduce the characteristics of the tumor microenvironment, thus limiting our understanding of cancer biology. In this context, three-dimensional (3D) models have emerged as representative tools that more accurately reproduce tissue architecture, cell signaling, and nutrients and oxygen gradients. These cellular models offer greater similarity to primary tissues, improving the study of relevant biological processes. Although 3D cultures provide numerous advantages in cancer research, there is no unified model that standardizes the matrix type and parameters such as gelation time or porosity, hindering the reproducibility and interpretability of the data. This review integrates evidence from various studies to evaluate the effect of epigenetic variations generated by 3D culture methods, which are regulated by mechanotransduction and, consequently, by signaling pathways such as integrin/FAK-ILK/Rho-YAP derived from interactions of cells with extracellular matrix-enriched scaffolds. This affects processes such as DNA methylation, histone coding, and the regulation of non-coding RNAs such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) in different molecular subtypes of breast cancer. Overall, the evidence highlights that 3D culture methods are not equivalent but rather generate distinct epigenetic signatures at the non-coding RNA level that influence the proliferation, differentiation, therapeutic resistance, and metastatic potential of tumor cells. Furthermore, the evidence suggests that histone coding patterns, primarily through the reduction of acetylation marks, are conserved regardless of the type of 3D culture. In summary, the study highlights that the microarchitectural and compositional characteristics of 3D scaffolds are key determinants of epigenetic plasticity. Full article

Exosome-derived microRNAs (miRNAs) have been proposed as minimally invasive biomarkers for laryngeal squamous- cell carcinoma (LSCC). Because oral and maxillofacial surgeons are integral to head-and-neck oncologic and reconstructive pathways, such liquid-biopsy signals could support perioperative decision-making (selection for organ-preserving surgery), margin surveillance, and reconstructive planning. We conducted a preregistered, protocol-driven search of PubMed/MEDLINE, Web of Science, and Scopus from inception to 1 June 2025. Given the very small number of clinically comparable diagnostic studies, discordant index tests/thresholds, and high heterogeneity, we did not perform quantitative pooling or publication-bias testing. Instead, we undertook a narrative synthesis and constructed an evidence map; risk of bias tools (QUADAS-2; ROBINS-I) were applied descriptively to inform qualitative confidence. Nine studies were formally analysed based on eligibility to the study topic. Two serum-based case–control investigations (111 LSCC, 80 controls) reported areas under the ROC curve of 0.876 (miR-21 + HOTAIR) and 0.797 (miR-941), with corresponding sensitivities of 94% and 82%. Seven mechanistic papers showed that vesicular cargos—including miR-1246, circPVT1, and LINC02191—drive STAT3-dependent M2 polarisation, NOTCH1-mediated stemness, Rap1b-VEGFR2 angiogenesis, and glycolytic re-programming, producing 1.6–2.6-fold increases in invasion, tube formation, or xenograft growth. Only three studies fulfilled MISEV-2018 characterisation criteria, and none incorporated external validation. This narrative review and evidence map identifies promising but preliminary diagnostic signals and biologically plausible mechanisms for exosomal miRNAs in LSCC; however, the evidence is sparse, single-region, methodologically inconsistent, and at high risk of bias. Findings do not support clinical implementation at this stage. Priorities include harmonised EV workflows, prespecified thresholds, and prospective, multi-centre validation. Full article

Kaposi’s sarcoma (KS), an AIDS-defining illness, is caused by Kaposi’s sarcoma-associated herpesvirus (KSHV). A member of the human herpesvirus family, designated as human herpesvirus 8 (HHV-8), KSHV is also linked to other oncogenic manifestations such as primary effusion lymphoma (PEL). The current dearth of available compounds against KSHV necessitates development of effective antiviral treatments. As with other herpesviruses, KSHV can result in both lytic and latent infections. KSHV pathogenesis and the development of KS have been associated with the expression of KSHV genes and transcripts during viral infections. The transcriptome of KSHV heavily intersects with regulatory pathways and mechanisms involved with a multitude of diseases in humans. Circular RNAs (circRNAs) have recently been discovered to be expressed by KSHV. Research endeavors on KSHV circRNAs have focused on the roles they play throughout latent and lytic infection. Understanding the specific functions and interactions of KSHV circRNAs with the viral and host transcriptomes, as well as how they are identified and analyzed, will be the primary focus of this review. Overall, recent advances in KSHV circRNA research have deepened our understanding of the KSHV transcriptome and pathogenesis and are paving the way for the development of circRNA-based antiviral therapies. Full article

The open reading frame 3 (ORF3) protein of the swine hepatitis E virus (SHEV) is a critical virulence factor implicated in viral infection, yet its precise mechanisms remain poorly understood. Circular RNAs (circRNAs) have emerged as key regulators of gene expression during viral infections by functioning as miRNA sponges. This study aimed to identify key circRNAs and construct a potential circRNA-miRNA-mRNA regulatory network associated with the viral infection pathway in HepG2 cells expressing genotype IV SHEV ORF3. Based on our previous high-throughput circRNA and transcriptome sequencing data from HepG2 cells with adenovirus-mediated ORF3 overexpression, we screened for differentially expressed circRNAs and mRNAs linked to viral infection pathways. Using bioinformatic tools, we predicted miRNAs targeted by these mRNAs and those that could bind to the circRNAs, ultimately constructing a competing endogenous RNA (ceRNA) network with Cytoscape. We identified 31 differentially expressed circRNAs and 7 mRNAs (HSPA8, HSPA1B, EGR2, CXCR4, SOCS3, NOTCH3, and ZNF527) related to viral infection. A potential ceRNA network comprising 32 circRNAs, 23 miRNAs, and the 7 mRNAs was constructed. Core circRNAs, including ciRNA203, circRNA14936, and circRNA5562, may act as miRNA sponges to regulate the expression of these mRNAs. This network suggests a novel mechanism by which SHEV ORF3 might modulate host cell functions to facilitate viral infection. Full article

Agriculture is still at serious risk from viral infections, particularly in light of climate change and more intensive farming practices. Small non-coding RNAs (sRNAs), in particular microRNAs (miRNAs) and circular RNAs (circRNAs), have emerged as crucial post-transcriptional regulators of plant antiviral defense in this setting. These molecules provide an essential RNA-based immunity layer by regulating hormones, autophagy, redox balance, immunological signaling, and programmed cell death. In this work, we examine the molecular processes through which circRNAs and miRNAs function during viral infection, focusing on how they affect autophagy and systemic acquired resistance (SAR). Through thorough searches of PubMed, Web of Science, and Scopus, we combined findings from peer-reviewed experimental and transcriptomic studies. Our study covers important crops as well as model species (Arabidopsis thaliana, Nicotiana benthamiana), providing a thorough understanding of sRNA synthesis, target control, and antiviral signaling. By combining previously disparate data, this review provides a coherent framework for understanding how short RNAs affect plant immune responses to viral infections. We highlight key regulatory relationships that need further study and propose that these results can be used as a foundation for new RNA-based biotechnological approaches. By carefully altering RNA regulatory mechanisms, scientists can use this information to help them create more resistant crops. Full article

Type 2 diabetes mellitus (T2DM) is characterized by an uncontrolled increase in blood glucose levels and insulin resistance in cells of various tissues. Vascular complications in T2DM have an inflammatory nature. Drugs with different mechanisms of action have been developed and used to treat T2DM, initially aimed at controlling blood glucose levels. Among them, sodium-glucose cotransporter 2 inhibitors (SGLT2-i) were developed as specific inhibitors of glucose reabsorption in the kidneys, but along with lowering blood glucose levels, they demonstrated multiple (including non-glycemic) positive effects in the treatment of T2DM related to their beneficial effects on the immune system. SGLT2 inhibitors can reduce the risk of diabetic cardiomyopathy (DCM) and chronic kidney disease (CKD) development in patients with and without diabetes. SGLT2-is improve cardio-renal complications through a number of signaling pathways, including those dependent on the involvement of non-coding RNAs (ncRNAs) and their targets. The best-studied classes of ncRNAs are microRNAs, which are short (less than 200 bases) RNAs (miRNAs), long non-coding RNAs (lncRNAs) (more than 200 bases), and circular RNAs (circRNAs). The regulatory effect of ncRNAs has broad physiological significance, and changes in the ncRNAs’ expression are associated with the pathogenesis of different diseases, including T2DM. RNA-seq allows the construction of networks of interactions of lncRNA/circRNA-miRNA-mRNA called competitive endogenous RNA (ceRNA) networks, to identify clinically significant molecular markers, to improve the mechanistic understanding of pathogenesis, and to contribute to the development of new diagnostics and therapies. Our review summarizes the role of non-coding RNA in the action of SGLT2 inhibitors in cardio-renal complications in T2DM. We focus on methods of detection, genetics, and the effects of non-coding RNA. Specific attention is given to the role of non-coding RNAs in the inflammatory reactions of innate immune cells in relation to the SGLT2 inhibitors. Full article