Aug 2026· The Journal of pharmacy and pharmacology· Vol 78 8· 0 citations
Medicine
TL;DR
This review consolidates current knowledge on MEG3, detailing its genetics, expression regulation, and core mechanisms-primarily its role as a competing endogenous RNA (posttranscriptional regulation) and as a scaffold for chromatin modifiers to modulate inflammatory pathways.
This work provides a comprehensive framework that clarifies recent controversies—such as whether H4K16ac primarily governs transcription or replication timing, and which KAT8-containing complex catalyzes, which acetylation mark—and establishes a rationale for future precision-targeting strategies and biomarker development grounded in KAT8 functional heterogeneity.
Ten-Eleven Translocation 2 (TET2) is a pivotal α-ketoglutarate and Fe2+-dependent dioxygenase belonging to the TET family, governing epigenetic homeostasis through DNA, RNA, and histone modifications. Its central function involves the iterative oxidation of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) and further derivatives, initiating active DNA demethylation. Beyond this, TET2 catalyzes RNA m5C oxidation and interacts with histone modifiers, thus modulating diverse cellular processes. Physiologically, TET2 is indispensable for hematopoietic stem cell (HSC) function, genomic stability, and the resolution of inflammation. Its dysregulation, often driven by somatic mutations, is implicated across a broad spectrum of human diseases. These include hematological malignancies, solid tumors, inflammatory disorders, cardiovascular diseases (CVD), metabolic abnormalities, and neurological conditions. Notably, TET2 exhibits strong context dependency, functioning as a tumor suppressor in myeloid malignancies while exerting distinct immunomodulatory roles in certain solid tumors. This review systematically summarizes recent advances in the molecular mechanisms and physiological functions of TET2, and highlights its disease-specific roles and promising therapeutic strategies. We also discuss unresolved challenges and future research directions to facilitate the clinical translation of TET2-related epigenetic findings.
Jingyi Tang, Ruoxian Wang, Li Long et al.· Frontiers in Immunology· 0 citations
Cancer remains a major global health burden, with its incidence and mortality rates persistently high despite advances in treatment. Despite therapeutic innovations, malignant tumors continue to pose a formidable challenge to global health. Against this backdrop, the crosstalk between long non-coding RNAs (lncRNAs) and the Notch signaling pathway has emerged as a pivotal driver of tumorigenesis and progression. However, the complex regulatory network and a comprehensive mechanistic framework of this axis await systematic elucidation. This review systematically consolidates recent advances in understanding how lncRNAs precisely modulate Notch pathway activity through diverse mechanisms, including acting as competing endogenous RNAs, direct protein binding, epigenetic regulation, and exosome-mediated intercellular communication. The discussion encompasses various malignancies, spanning the digestive, respiratory, urogenital, nervous, and hematologic systems. The lncRNA-Notch regulatory axis is identified as a ubiquitous and functionally central oncogenic network. It orchestrates critical malignant phenotypes—such as such as stemness maintenance, epithelial-mesenchymal transition, metabolic shifts, drug resistance, and immune evasion—through intricate bidirectional crosstalk. Functional studies confirm that targeting key nodes of this axis can effectively reverse drug resistance and suppress tumor growth. Although challenges remain in its clinical translation, future research integrating single-cell multi-omics, nanotechnology, and other innovative strategies will undoubtedly open new avenues for precision diagnosis and cancer therapy.
Qing-miao Shi, Na Lou, Huiwu Xing et al.· Frontiers in Cell and Develo...· 0 citations
Background: Asthma affects more than 300 million people worldwide and remains poorly controlled in a substantial proportion of patients despite available pharmacotherapy. Heterogeneity across allergic eosinophilic, neutrophilic, and mixed endotypes underscores the need for precise molecular tools. MicroRNAs (miRNAs)—small, ~22-nucleotide non-coding RNAs—have emerged as key modulators of immune polarization, airway epithelial integrity, airway smooth-muscle remodeling, and glucocorticoid responsiveness.
Objective: This narrative review examines the mechanistic roles of major asthma-associated miRNAs, evaluates circulating and extracellular-vesicle (EV) miRNAs as clinical biomarkers, and appraises preclinical therapeutic modulation strategies.
Key Findings: Among the most consistently implicated miRNAs, miR-21 promotes Th2 polarization via IL-12p35 suppression and amplifies steroid resistance through PI3K-mediated suppression of histone deacetylase 2 (HDAC2); it also enhances PI3K-Akt signaling by targeting PTEN, contributing to airway smooth-muscle proliferation and migration. miR-155 drives eosinophilic inflammation through PU.1 suppression, while miR-146a/b exert context-dependent anti-inflammatory effects that may be attenuated during viral exacerbations. The let-7 family maintains epithelial homeostasis and is downregulated in asthmatic airways. Biomarker studies in small case-control cohorts report potentially useful diagnostic signals (e.g., AUC = 0.91 for serum exosomal miR-155 in one moderate-to-severe asthma study); these are exploratory estimates from individual studies lacking external validation. Preclinical evidence supports antagomir-21 restoration of steroid sensitivity, miR-146a mimic attenuation of rhinovirus-induced inflammation, and mucus-penetrating EV delivery of miR-511-3p reversing allergic airway inflammation in murine models.
Conclusions: No completed asthma-specific miRNA therapeutic trial was identified. Translation requires multicenter biomarker validation, standardized pre-analytical workflows, human mechanistic studies, phenotype-stratified trial designs, and reproducible pulmonary delivery systems capable of cell-specific target engagement.
Siddarth Raajasekar· Genetics and Molecular Resea...· 0 citations
The NLRP3 inflammasome is a central regulator of innate immunity and inflammation, but its functions extend beyond a simple pro-inflammatory role. Increasing evidence indicates that the biological consequences of NLRP3 activation are highly context-dependent, with protective or pathogenic effects determined by cellular composition, tissue microenvironment, and disease stage. In this review, we examine NLRP3 biology across three interconnected dimensions: cellular context, including immune and non-immune compartments; microenvironmental context, including infectious versus sterile inflammation and tissue repair versus tissue damage; and disease context, including stage- and time-dependent functional shifts. We further discuss three major determinants of NLRP3 output: cytokine bias between IL-1β and IL-18, cell-fate decisions between pyroptosis and survival, and epigenetic programming of inflammasome-responsive states. Using representative disease settings such as cancer, inflammatory bowel disease, and autoimmune disorders, we illustrate how similar NLRP3 activation can lead to divergent biological outcomes. We also discuss the therapeutic implications of this plasticity, arguing that effective intervention will require context-selective rather than universal inhibition. A more precise understanding of NLRP3 context dependence may support rational trial design, biomarker development, future patient-stratification frameworks, and more biologically informed therapeutic strategies in NLRP3-related diseases.
Shuo Liu, Xun Liu, Jing Hu et al.· Journal of Translational Med...· 0 citations
The clinical heterogeneity of diabetic kidney disease (DKD) poses a major challenge to current treatment strategies. This review proposes a novel translational paradigm: viewing ion channels as dual-function entities that serve both as pathogenic mediators and as rich sources of clinically actionable biomarkers. We systematically elucidate how hyperglycemia, oxidative stress, and inflammation disrupt sodium, calcium, potassium, and chloride channel networks through interconnected pathways such as AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR), NLR family pyrin domain containing 3 (NLRP3), and PIEZO1. These disruptions not only drive renal injury but also generate a cascade of detectable molecular signals - from genomic variations and epigenetic changes to circulating protein fragments and exosomal non-coding RNAs. We review these multi-level biomarker sources and their detection platforms, including cutting-edge, minimally invasive technologies such as urinary cell-free DNA (cfDNA) methylation profiling and artificial intelligence (AI)-driven multi-omics integration. Crucially, we detail how these "channelopathy fingerprints" can be translated into clinical tools for molecular endotyping, predicting and monitoring treatment responses to established (sodium-glucose cotransporter 2 (SGLT2) inhibitors, finerenone) and emerging (transient receptor potential canonical 6 (TRPC6) inhibitors) therapies, and optimizing clinical trial designs through biomarker-driven enrichment strategies. Finally, we propose a phased, multi-stakeholder roadmap from biomarker discovery to clinical integration, aiming to shift DKD management from a "one-size-fits-all" approach to individualized precision therapy.
Xi Xiong, Bao Yan, Bin Ke et al.· American journal of translat...· 0 citations
