Search Results (104)

Host microRNAs (miRNAs) are widely proposed as innate antiviral effectors against SARS-CoV-2, yet whether they actually restrict infection in lung epithelial cells remains unresolved. Two of the most-cited candidates, miR-29a-3p and miR-15b-5p, are predicted to bind both the viral genome and key entry/trafficking factors such as Furin and ATG9A, but functional evidence is fragmented and often contradictory. Here, we put both miRNAs to the test in human Calu-3 cells infected with the SARS-CoV-2 Beta and Omicron BA.1 variants, using parallel gain- and loss-of-function strategies coupled to RT-qPCR of viral and cellular transcripts and back-titration of infectious progeny on VeroE6/TMPRSS2 cells. Both miRNAs transiently suppressed viral gene expression at 6 hpi, but this early dampening was followed by a marked transcript rebound at 24 hpi, especially for Omicron, with virtually no impact on total extracellular viral RNA. More strikingly, miR-15b modulation enhanced infectious virus output during Beta infection, and miR-29a overexpression boosted Omicron BA.1 infectivity, while Furin, ATG9A, AKT3, and TFEB showed only modest, condition-dependent shifts. Rather than acting as clean antiviral effectors, miR-29a and miR-15b emerge as context-dependent modulators that can paradoxically favor SARS-CoV-2 replication—a cautionary signal for miRNA-based antiviral strategies. Full article

Background: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and is strongly associated with atrial structural remodeling driven by activated cardiac fibroblasts. Autophagy has been implicated in AF-related atrial remodeling; however, the non-coding RNA mechanisms that govern autophagic activation in atrial fibroblasts under rapid electrical stress remain poorly understood. Methods: Human cardiac fibroblasts from adult atria (HCF-aa) were subjected to rapid electrical stimulation (RES) at 0.5 V/cm and 10 Hz. Expression levels of exosomal metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), cytoplasmic miR-204-5p, and microtubule-associated protein light chain 3B (LC3B) were measured using quantitative real-time PCR and Western blot analyses. Luciferase reporter assays were performed to confirm direct molecular interactions. The functional roles of MALAT1 siRNA, miR-204-5p mimics/antagomirs, rapamycin, and 3-methyladenine (3-MA) on LC3B expression and autophagic activation were assessed by Western blot and immunofluorescence confocal microscopy for LC3B puncta formation. Results: RES significantly induced exosomal MALAT1 expression in a voltage- and time-dependent manner, peaking at 2 h post-stimulation, while cytoplasmic MALAT1 levels remained unchanged. Cytoplasmic miR-204-5p exhibited an initial transient rise followed by a significant decline at 2 h, inversely correlating with peak MALAT1 levels. LC3B mRNA and protein expression subsequently increased, peaking at 6 and 16 h, respectively. Luciferase reporter assays confirmed that miR-204-5p directly binds both the MALAT1 transcript and the 3′-UTR of LC3B mRNA. MALAT1 knockdown augmented miR-204-5p levels and suppressed LC3B expression, while miR-204-5p overexpression attenuated RES-induced LC3B upregulation and LC3B puncta accumulation. Conversely, miR-204-5p inhibition further enhanced autophagic activation, as evidenced by increased LC3B puncta density. Conclusions: In HCF-aa subjected to RES, MALAT1 functions intracellularly as a competing endogenous RNA to putatively sequester miR-204-5p, thereby de-repressing LC3B expression and promoting autophagic activation. Concurrent exosomal secretion of MALAT1 may additionally serve as a paracrine signal to neighboring cells, though this requires future conditioned-media transfer experiments to confirm. Full article

Long non-coding RNAs (lncRNAs) have emerged as important regulatory molecules in plants, but their potential roles during modern maize breeding remain largely unexplored. This study systematically characterized lncRNA expression dynamics using transcriptome data from 137 maize inbred lines from different breeding eras in China. We identified 18,023 lncRNAs transcripts, grouped by expression trends across historical breeding eras. Comparative analysis revealed 2228 differentially expressed lncRNAs transcripts (DElncRNAs) between modern (CN2000&10s) and early (CN1960&70s) accessions. By integrating WGCNA and cis-target analysis, we identified candidate lncRNAs and putative lncRNA-PCG associations that may be associated with maize plant architecture-related processes. Further, 771 DElncRNAs were predicted to be associated with 810 protein-coding genes, and these associated genes were significantly enriched in plant hormone signal transduction. Dual-luciferase reporter assays provided preliminary experimental support that lncrna.33063 and lncrna.33068 can repress the promoter activity of ZmPIF5.2 in a heterologous transient expression system. Furthermore, we constructed a putative ceRNA-related candidate interaction network consisting of lncRNA–miRNA–mRNA triplets that include 317 candidate miRNA-lncRNA pairs and 8325 candidate miRNA-mRNA pairs, with the associated mRNAs enriched in biological processes such as morphogenesis, stimulus response, and hormone metabolism. These findings provide a set of candidate lncRNAs and lncRNA-PCG associations for future functional validation and may offer useful clues for understanding the possible roles of lncRNAs in agronomic trait-related biological processes and maize molecular breeding. Overall, this study provides candidate genetic resources and a framework for future investigation of lncRNA-associated relationships potentially related to agronomic trait variation in maize. Full article

Apoptosis maintains tissue homeostasis, and its dysregulation is closely associated with breast cancer progression and therapeutic resistance. We performed an integrative analysis of apoptosis-related signaling in breast cancer tissues across five molecular subtypes and compared these patterns with systemic apoptotic responses following cryoablation of benign fibroadenomas. Gene expression profiling was conducted using mRNA microarrays and validated by qRT-PCR and ELISA. Apoptosis pathway activity was assessed with the MSigDB HALLMARK_APOPTOSIS gene set, including intrinsic and extrinsic pathway scoring and an apoptotic balance index (ABI). MicroRNA profiling combined with in silico analyses identified potential miRNA–mRNA interactions. A progressive shift toward reduced pro-apoptotic and enhanced stress-adaptive signaling was observed with increasing tumor aggressiveness, most pronounced in triple-negative and non-luminal HER2-positive cancers. This pattern included reduced intrinsic pathway activity, decreased ABI, downregulation of pro-apoptotic genes (BIK, BMF, TXNIP), and upregulation of stress-associated or cytoprotective genes (HSPB1, PPT1). Several expression patterns were accompanied by overexpression of miRNAs (miR-582-5p, miR-421, miR-106b-5p, miR-20a-5p, miR-20b-5p, miR-93-5p) predicted to target apoptosis-related genes. In contrast, fibroadenoma cryoablation was associated with transient systemic modulation of apoptosis-related genes and proteins followed by gradual normalization. These findings highlight differences between apoptosis-related dysregulation in malignant tissue and regulated systemic responses following benign tissue injury, supporting pathway-level interpretation and identifying candidate molecular networks warranting further mechanistic and translational investigation. Full article

Ferroptosis is an iron-dependent form of regulated cell death driven by lipid peroxidation and oxidative stress, increasingly implicated in cancer biology. However, its molecular regulation across breast cancer subtypes and its potential systemic manifestations remain incompletely understood. The aim of this study was to identify ferroptosis-associated molecular alterations that are largely shared across subtypes and to evaluate their systemic reflection following localized tissue injury. Tumor and matched normal breast tissues representing major molecular subtypes were analyzed. Global mRNA and miRNA expression profiling was performed using microarrays, followed by validation of selected genes using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA). Functional enrichment and protein–protein interaction analyses were conducted to characterize associated pathways. In addition, systemic responses were assessed in patients undergoing fibroadenoma cryoablation through longitudinal blood sampling. Six ferroptosis-related genes (SLC7A11, GPX4, FTH1, NQO1, NFE2L2, SQSTM1) demonstrated consistent upregulation across all breast cancer subtypes, with higher expression observed in more aggressive tumors. These genes are functionally linked to antioxidant defense, iron metabolism, and oxidative stress regulation, and their coordinated expression pattern is consistent with activation of NRF2-dependent cytoprotective pathways. Downregulation of selected miRNAs may contribute to this expression profile but likely represents a secondary regulatory mechanism. Survival analysis revealed heterogeneous and subtype-dependent associations, with limited and gene-specific prognostic relevance. Cryoablation induced transient increases in circulating levels of the analyzed proteins, reflecting systemic responses to localized tissue injury. In conclusion, breast cancer is characterized by a largely shared ferroptosis-associated molecular signature across subtypes; however, its clinical impact appears to be variable and context-dependent. Systemic detection of related molecular signals suggests potential utility as indicators of tissue stress responses, although their role as specific biomarkers of ferroptosis requires further validation. Full article

Intermediate monocytes (CD14⁺⁺CD16⁺), a highly pro-inflammatory subset, are linked to endothelial activation, thrombus formation, and poor outcomes in acute coronary syndrome (ACS), suggesting a role in the transition to plaque vulnerability. MicroRNA-92a (miR-92a) promotes vascular inflammation by repressing the transcription factors Kruppel-like factors (KLFs) 2/4, thereby inducing endothelial dysfunction and increasing leukocyte adhesion. Because both intermediate monocytes and miR-92a contribute to plaque instability, their expression profiles appear relevant in acute ischemia. We investigated whether miR-92a is differentially regulated in monocyte subpopulations in ACS compared to chronic coronary syndrome (CCS). Patients with ACS (STEMI/NSTEMI) undergoing urgent coronary angiography and patients with CCS were enrolled. Blood samples were collected peripherally (T_0P) and from the culprit coronary artery (T_0C) during catheterization. Additional peripheral samples were collected 48 h after intervention (T₁) and at the 3-month follow-up (T₂). Peripheral blood mononuclear cells (PBMCs) were isolated by Ficoll density-gradient centrifugation. Monocytes were sorted by fluorescence-activated cell sorting (FACS) into classical (CD14⁺⁺CD16^–), intermediate (CD14⁺⁺CD16⁺), and non-classical (CD14⁺CD16⁺⁺) subsets. MiR-92a expression was measured using real-time PCR and analyzed across predefined time points. In classical and non-classical monocytes, miR-92a levels remained stable throughout the observation period and did not differ between ACS and CCS patients. No spatial expression gradient was observed between intracoronary and peripheral samples at baseline. In contrast, intermediate monocytes in the ACS cohort showed a transient increase in miR-92a expression at T₁ compared with baseline (T_0p) and the 3-month follow-up (T₂). No comparable temporal changes were observed in CCS patients. These findings indicate a temporary alteration of miR-92a expression in intermediate monocytes during the early post-interventional phase following ACS. However, given the exploratory nature of this study and the limited sample size, the biological significance of this observation requires confirmation in larger cohorts. Full article

Salt, drought and freezing stress were major abiotic factors limiting plant growth, development and yield. Halostachys caspica (Amaranthaceae), a halophyte native to saline-arid desert regions, tolerated multiple abiotic stresses, but its molecular mechanisms of stress tolerance remain unclear. By integrating the small RNA library and transcriptome data of H. caspica under high salinity, HcmiR172e was identified as a differentially expressed miRNA and selected for the study of multiple abiotic stress responses. Using its mature sequence (20 nt) to align with upregulated genes from the transcriptome, HcTOE3 (AP2 subfamily transcription factor belonging to the AP2/ERF family) was preliminarily predicted as its target gene through bioinformatic analysis. Our previous work demonstrated that HcTOE3 was strongly upregulated by multiple abiotic stresses, including salinity, drought, heat and low temperature. Furthermore, overexpression of HcTOE3 conferred freezing tolerance to Arabidopsis throughout the entire growth period. In this study, miRNA expression analyses showed that HcmiR172e was significantly downregulated in the assimilating branches of H. caspica under low temperature, heat, salt, drought, oxidative stress and abscisic acid (ABA) application. Tobacco transient expression assays and 5′RLM-RACE confirmed that HcmiR172e directly cleaved HcTOE3 transcripts in the region close to the 5′end of the ORF. HcmiR172e-overexpressing Arabidopsis displayed increased sensitivity to salt, drought, freezing stresses and ABA treatment, along with enhanced growth inhibition, elevated reactive oxygen species (ROS) accumulation, decreased osmolyte content and downregulation of stress-responsive genes. In contrast, HcTOE3-overexpressing Arabidopsis exhibited the opposite phenotypes, physiological responses and corresponding gene expression patterns under multiple stress treatments. These findings collectively elucidated the antagonistic regulatory roles of HcmiR172e and HcTOE3 in plant abiotic stress responses, providing novel molecular targets for engineering stress-tolerant crops for saline, arid, freezing environments. Full article

MicroRNA-122 (miR-122) is the most abundant hepatic microRNA and a key regulator of hepatocyte proliferation, metabolism and differentiation. Although widely studied in hepatocellular carcinoma, its role in liver regeneration remains unexplored. This study investigated how miR-122 deficiency modulates liver regeneration under physiological conditions and during chronic liver injury. A miR-122-deficient mouse model (miR-122^−/−) was generated using CRISPR/Cas9, and liver regeneration was assessed after two-thirds partial hepatectomy (PHx) in healthy and CCl₄-induced fibrotic livers. In healthy liver, miR-122 expression was transiently downregulated within 24 h after PHx, suggesting a physiological role in cell cycle entry. After PHx in non-fibrotic livers, miR-122^−/− mice showed increased basal proliferation and accelerated regeneration, associated with Cyclin D1 and RhoA overexpression, enhanced cytokinesis and a predominance of diploid hepatocytes. In contrast, miR-122 deficiency markedly exacerbated CCl₄-induced fibrosis, leading to cirrhosis-like architecture, impaired hepatocyte function, and severe metabolic dysregulation. Despite increased proliferation after PHx, fibrotic miR-122^−/− mice exhibited severely impaired regeneration and near-complete mortality. Proteomic analyses revealed metabolic failure, oxidative stress, and inflammatory activation, creating an unfavorable environment for tissue repair. In conclusion, miR-122 plays a dual role in liver regeneration. While its suppression enhances regeneration in healthy liver, loss of miR-122 under fibrotic conditions drives pathological repair, metabolic failure and lethality, highlighting its critical role in chronic liver disease. Full article

Objective: Rare-earth elements are extensively employed across diverse industrial sectors, increasingly raising concerns about their potential health hazards in both occupational and environmental contexts. Samarium oxide (Sm₂O₃), a routinely processed rare-earth product, reproducibly precipitates pulmonary fibrosis in experimental models, yet the molecular circuitry that transduces its fibrogenic signal remains almost entirely unmapped. This study aims to elucidate the role of miR-214-3p in Sm₂O₃-induced pulmonary fibrosis and to investigate its regulatory mechanism at the molecular level. Methods: A murine model of pulmonary fibrosis was established via intratracheal instillation of Sm₂O₃, and histopathological changes were assessed using hematoxylin and eosin (H&E) and Masson’s trichrome staining. RNA sequencing was performed on lung tissues to identify differentially expressed mRNAs. Leveraging our previously generated miRNA landscape of Sm₂O₃-exposed lungs, we subjected the dataset to Gene Ontology and KEGG enrichment analyses, which convergently identified miR-214-3p as the top-ranking candidate regulator of the fibrogenic MAPK axis. The direct targeting of MAP2K3 by miR-214-3p was validated using a dual-luciferase reporter assay. Expression levels of fibrotic markers (α-SMA, Collagen I) and key components of the MAPK signaling pathway (MAP2K3, p-MAPK14, MST1) were quantified in both in vivo and in vitro models using qRT-PCR and Western blotting. Gain- and loss-of-function studies, complemented by rescue assays, were performed in human embryonic lung fibroblasts (HELFs) via transient transfection of miR-214-3p mimics, inhibitors, or MAP2K3-overexpression plasmids. Cell proliferation was evaluated using the EdU assay, and TGF-β1 secretion was measured by ELISA. Results: Sm₂O₃ exposure induced significant pulmonary fibrosis in mice, accompanied by marked downregulation of miR-214-3p and upregulation of MAP2K3 in lung tissues. Overexpression of miR-214-3p or silencing of MAP2K3 effectively suppressed Sm₂O₃-induced fibroblast activation, including reduced cell proliferation, decreased expression of α-SMA and Collagen I, and inhibition of p38 MAPK phosphorylation. Notably, ectopic overexpression of MAP2K3 reversed the protective effects conferred by miR-214-3p, confirming a functional rescue. Conclusions: miR-214-3p directly silences MAP2K3, thereby blunting p38 MAPK-driven fibrogenesis after Sm₂O₃ exposure. Our data unveil a miR-214-3p–MAP2K3–p38 MAPK axis that constitutes a readily druggable target for rare-earth-element-induced pulmonary fibrosis. Full article

The WRKY transcription factors (TFs) are key regulators of plant responses to biotic and abiotic stresses. However, their roles in Amaranthus palmeri remain unexplored. In this study, 32 ApWRKYs were identified through bioinformatics and gene expression analyses. Subcellular localization predictions placed ApWRKYs in the nucleus, and transient expression assays of ApWRKY2 and ApWRKY5 confirmed nuclear targeting, supporting their role as transcriptional regulators. ApWRKYs are distributed across 15 genomic scaffolds, and phylogenetic analysis grouped them into three subfamilies, with conserved motifs identified within specific clades. Interaction analysis suggested potential post-transcriptional regulation by miRNAs. Gene expression profiling of ApWRKYs under glufosinate ammonium, NaCl, and PEG-induced osmotic stress treatments revealed potential distinct regulatory roles. Furthermore, transient overexpression in Arabidopsis thaliana found that ApWRKY1, ApWRKY2, and ApWRKY5 potentially regulate chlorophyll fluorescence and photosynthetic efficiency under glufosinate treatment. These findings establish ApWRKYs as central regulators of stress adaptation in A. palmeri, provide novel insights into WRKY-mediated regulation, and lay a foundation for future functional investigations aimed at enhancing stress resilience and herbicide management in horticultural systems. Full article

Epigenetic dysregulation is a central driver of cancer progression, therapeutic resistance, and phenotypic plasticity. Among epigenetic mechanisms, microRNAs (miRNAs) and DNA methyltransferases (DNMTs) engage in reciprocal regulatory interactions that extend beyond transient gene control. Emerging evidence indicates that DNMT–miRNA feedback loops function as epigenetic memory units, stabilizing malignant cell states and enabling durable phenotypic inheritance even after removal of initiating stimuli under conditions shaped by persistent redox and stress signaling cues. In this review, we synthesize mechanistic, computational, and translational studies demonstrating how double-negative DNMT–miRNA feedback architectures generate bistable regulatory circuits that lock cancer cells into epithelial–mesenchymal transition, stem-like, and therapy-resistant states through redox-sensitive regulatory thresholds rather than static epigenetic alterations. This framework provides a unifying explanation for why transient environmental or therapeutic cues can induce long-lasting epigenetic reprogramming and why conventional single-target epigenetic inhibitors often fail to achieve durable clinical responses. Building on this concept, we propose that herbal medicines and plant-derived phytochemicals act as epigenetic reset signals capable of destabilizing pathological epigenetic attractor states encoded by DNMT–miRNA memory circuits by modulating intracellular redox balance and redox-responsive signaling pathways. Owing to their multi-component and systems-level regulatory properties, herbal interventions modulate miRNA expression, DNMT activity, and upstream stress-responsive pathways in a coordinated manner, facilitating transitions from memory-dominated states toward renewed epigenetic plasticity. We further discuss the translational implications of combining miRNA-based therapies with herbal medicine as a strategy for epigenetic reprogramming rather than transient suppression within a redox-guided therapeutic framework. Finally, we address key challenges and clinical feasibility considerations, including delivery, heterogeneity, and safety, and outline future directions for biomarker-guided and systems-informed epigenetic therapies that incorporate redox state as a functional determinant of epigenetic responsiveness. By reframing DNMT–miRNA interactions through the lens of epigenetic memory, this review highlights miRNA–herbal combination strategies as a forward-looking approach for overcoming therapeutic resistance and achieving durable reprogramming in cancer through selective manipulation of redox-sensitive epigenetic signaling circuits. Full article

JNJ-26366821, a novel thrombopoietin mimetic peptide (TPOm), is shown to increase platelets (PLTs) transiently in peripheral blood. We hypothesized that increases in PLT counts may involve stimulation of hematopoiesis via induction of cytokines, growth factors, and microRNAs. Hence, we measured various cytokines, chemokines, and growth factors in serum. Time-course analysis of G-CSF, IL-5, IL-6, IL-9, IL-10, TNFα, IL-1α, and IL-1β expression was significantly altered in the control group at 9.5 Gy compared to a lower non-lethal dose of 7 Gy on days 7 to 15 post-exposure. TPOm pre-treatment significantly ameliorated the changes in expression of these pro-inflammatory cytokines and growth factors. Additionally, we show that TPOm differentially modulates the miRNA expression profiles in the spleen of irradiated mice compared to controls at both early times as well as later times after irradiation. These results suggest a possible role of TPOm in protecting animals from radiation-induced thrombocytopenia and lethality by attenuating radiation-induced inflammatory cytokines and miRNAs. Full article

Background/Objectives: Biotin plays important roles in critical metabolic reactions and also contributes to the regulation of gene expression. While its role in regulating gene expression via transcriptional/epigenetic mechanisms is well established, little is known about its ability to regulate expression at the post-transcriptional level. Methods: To address this, we examined how biotin deficiency affects microRNAs (miRNAs) expression in the colon, a tissue that is impacted by deficiency of this micronutrient. Results: We identified (by miRNA sequencing) 26 miRNAs whose expression was significantly altered in the colon of biotin-deficient mice compared with pair-fed controls. Among these, ten miRNAs with known roles in mucosal physiology and inflammation were selected for direct validation, and their altered expression patterns were confirmed by RT-qPCR. In silico analyses further revealed that important proteins involved in maintaining normal colonic function (the tight junction protein ZO1 and the stem cell marker LGR5) and in mediating inflammation (NLRP3 and calprotectin), all of which are dysregulated in biotin deficiency, possess putative binding sites on 3′-UTR for several of the altered miRNAs. Moreover, transient transfection of miR-190a-5p and miR-199a-5p, whose expression was upregulated during biotin deficiency and predicted to target ZO1 and LGR5, respectively, in human colonic NCM460 cells, led to a significant reduction in the level of the corresponding mRNAs, confirming functional regulation of these targets. IPA further showed that the differentially expressed miRNAs are associated with gastrointestinal and inflammatory disease pathways. Conclusions: Findings of this investigation show that biotin deficiency disrupts colonic miRNA expression, potentially contributing to downstream alterations in important physiological and inflammatory protein expression. Full article

Background/Objectives: High-risk, low-frequency incidents such as building collapses and large chemical fires can result in acute, high-dose exposures to toxic agents for first responders and the surrounding community. While these exposures may last for hours to days, their contribution to firefighters’ risks for cancer and other diseases is relatively unknown. In February 2023, a freight train transporting chemicals derailed and caught fire in East Palestine, Ohio, US. More than 350 firefighters, primarily volunteer, responded to the incident. In this cross-sectional study, we evaluated epigenetic markers of toxicity in responding firefighters. We hypothesized that exposures from responding to the train derailment would alter the expression of microRNAs (miRNAs) linked to carcinogenesis. Methods: We enrolled 62 responding firefighters and a comparison group of 26 firefighters from the same region who did not respond to the incident. We measured the relative expression of 800 miRNAs in blood samples using the nCounter Human v3 miRNA expression panel. We compared the expression of miRNA between exposure groups in negative binomial regression models, adjusting for potential confounders. Results: At a false discover rate cut-off of 5% (q-value < 0.05), 16 miRNAs had significantly higher expression and one significantly lower among firefighters that responded to the incident. Top disease-related pathways in which these miRNAs were enriched included those relevant to neurodegenerative diseases, vascular disease, and multiple cancer sites. Conclusions: Overall, results suggest responding to one large incident can have non-transient impacts on miRNA expression. Whether this translates into longer-term health risks or adaptive responses to exposures is unclear. Full article

Myocardial infarction (MI) triggers complex pathological processes, including inflammation, hypoxia, and fibrotic remodeling. MicroRNAs (miRNAs) have emerged as promising biomarkers for cardiovascular injury; however, their expression dynamics along processes remain underexplored. We used an in vivo rat model of permanent coronary occlusion to study the molecular alterations associated with MI and its resolution in a temporal mode, including five experimental groups with five animals in each: sham, PO 24 h, PO 72 h, PO 7 d, PO 1 month. Histological analysis, serum biomarkers, and miRNA/gene expression profiles were analyzed in a time-dependent manner post-occlusion. Subsequent analysis revealed early depletion of selected circulating miRNAs (PO 24 h). Transient upregulation in cardiac tissue miRNAs, inflammatory and fibrotic gene expression (Fibronectin, Collagen, Vimentin, E-Cadherin) were observed at PO 72 h. These molecular alterations correlated with histological evidence of myocardial injury and repair. Taken together, our findings delineate the molecular timeline of MI progression and resolution and identify candidate miRNAs as sensitive and time-dependent indicators of myocardial stress, including miR-107, miR-122-5p and miR-221-3p. This integrative approach supports the use of miRNA signatures for noninvasive monitoring of cardiac injury and resolution and unveils potential therapeutic targets to reduce pathological remodeling. Full article