Search Results (4,613)

Background/Objectives: While currently termed premature ovarian insufficiency (POI), premature ovarian failure (POF) remains a prominent driver of female infertility with a molecular pathogenesis that is still lacking comprehensive clarification. In in vitro studies, the pathology of POI is commonly simulated through a well-characterized model involving VCD (4-vinylcyclohexene diepoxide)-mediated cytotoxicity within KGN-derived human granulosa cells. However, the key regulatory molecular networks involved in this process are still poorly characterized. Although microRNAs (miRNAs) have emerged as critical regulators in ovarian function decline, the specific role and underlying mechanism of miR-27b-3p in POI remain elusive. Methods: A VCD-induced KGN cell injury model was established by treating cells with 1.0 mM VCD for 24 h. Cell viability, apoptosis rate, and miR-27b-3p expression were assessed by CCK-8 assay, flow cytometry, and RT-qPCR, respectively. Overexpression and targeted suppression of miR-27b-3p were achieved by introducing its specific mimics and inhibitors, respectively. Target identification was conducted via bioinformatic prediction, EdU incorporation, Western blot, and dual-luciferase reporter assays. Functional rescue experiments were carried out by co-transfection with a PAPPA-overexpressing plasmid (oe-PAPPA). IGF-1 secretion was quantified by ELISA, and phosphorylation of IGF1R and AKT was analyzed by Western blot to determine whether miR-27b-3p modulates cellular phenotypes via the PAPPA–IGF-1–PI3K/AKT axis. Exogenous IGF-1 supplementation was further applied to confirm pathway dependence. Results: VCD treatment dose-dependently restrained cellular growth and stimulated apoptotic pathways in KGN cells; paralleling these phenotypic changes, miR-27b-3p abundance was remarkably increased. Ectopic expression of miR-27b-3p exacerbated VCD-induced growth inhibition and apoptosis, whereas its inhibition conferred cytoprotective effects. Through the integration of computational predictions and dual-luciferase reporter systems, PAPPA was definitively established as a direct downstream target of miR-27b-3p. miR-27b-3p negatively regulated both PAPPA mRNA and protein levels, thereby impairing PAPPA-mediated cleavage of IGF-binding proteins (e.g., IGFBP4) and subsequent release of free IGF-1. This led to reduced IGF-1 secretion and significantly diminished phosphorylation of IGF1R and AKT. Remarkably, PAPPA overexpression effectively reversed the detrimental effects of miR-27b-3p, and exogenous IGF-1 supplementation similarly attenuated miR-27b-3p–mediated proliferation arrest and pro-apoptotic phenotypes. Conclusions: This study uncovers a novel pathogenic mechanism whereby miR-27b-3p exacerbates VCD-induced granulosa cell injury by directly targeting PAPPA, suppressing IGF-1 release, and consequently inhibiting the PI3K/AKT pro-survival signaling pathway. A novel perspective on the fundamental basis of POI is established by this research, which further posits therapeutic manipulation of the miR-27b-3p/PAPPA/IGF-1 module as a prospective treatment for disrupted ovarian function. Full article

MicroRNAs (miRNAs) are key regulators of gene expression that act primarily by binding to target messenger RNAs (mRNAs). However, the biology of miRNAs is more complex than initially thought, with functional complexity extending beyond canonical sequences. A multilayered miRNA regulatory landscape involving isomiR generation, altered 5p/3p strand usage, arm switching, A-to-I RNA editing, and epitranscriptomic RNA modifications operates in eukaryotic cells to regulate miRNA function. Collectively, these mechanisms expand the functional diversity of miRNAs by regulating their biogenesis, stability, strand selection, and target specificity, increasing their functional plasticity and contributing to regulatory heterogeneity found in cells. IsomiRs arise from alternative Drosha/Dicer processing, terminal nucleotide additions, RNA editing, and genetic variation, producing functionally distinct isoforms. Arm switching alters gene regulatory outputs through context-dependent changes in predominant 5p/3p strand usage. In addition, epitranscriptomic RNA modifications, such as m6A and m5C, together with A-to-I RNA editing, represent an additional layer of miRNA regulation. These mechanisms can act directly on miRNAs or their precursors, or indirectly by modifying circRNAs and lncRNAs, thereby altering miRNA availability and function. Together, these processes form a dynamic regulatory network that influences key cancer hallmarks, including cell proliferation, apoptosis, epithelial–mesenchymal transition, metastasis, immune evasion, and therapy resistance. However, the contribution of these non-canonical regulatory layers to tumor-specific miRNA function remains poorly understood. In this review, we explore how isomiR generation, miRNA strand selection, arm switching, and epitranscriptomic regulation expand the functional diversity of miRNAs in gynecologic cancers. Full article

MicroRNAs (miRNAs) have emerged as promising biomarkers for treatment response prediction in breast cancer. However, the role of circulating and tumour-derived miRNAs in predicting pathological complete response (pCR) following neoadjuvant therapy in HER2-positive (HER2+) breast cancer remains incompletely defined. To systematically evaluate the association between miRNA expression profiles and pCR in HER2+ breast cancer undergoing neoadjuvant systemic therapy, including chemotherapy with HER2-targeted agents. A systematic review of PUBMED, EMBASE, SCOPUS, and WEB OF SCIENCE databases was performed according to PRISMA guidelines. Studies evaluating circulating or tumour-derived miRNAs associated with pCR following neoadjuvant therapy in HER2+ breast cancer were included. Methodological quality was assessed using the QUIPS tool. Nine studies involving 937 HER2+ breast cancer patients were included. Overall, 39 unique miRNAs and four circulating miRNA signatures were associated with pCR outcomes. Seven studies evaluated circulating miRNAs, while two assessed tumour-derived miRNAs. The increased expression of six circulating miRNAs, four circulating signatures, and seventeen tumour-derived miRNAs was associated with pCR. Conversely, the increased expression of eleven circulating miRNAs and five tumour-derived miRNAs was associated with residual disease and non-pCR. MiR-210 was the only miRNA associated with response across more than one study, with an increased expression associated with residual disease in both circulating and tumour-derived analyses. Several circulating and tumour-derived miRNAs demonstrate potential as predictive biomarkers of pCR following HER2-targeted neoadjuvant therapy. However, substantial heterogeneity and limited validation currently restrict clinical implementation. Future prospective multicentre studies using standardised methodologies are required to clarify the role of miRNA profiling in personalised treatment strategies for HER2+ breast cancer. Full article

This study aimed to examine position-specific associations of contextual factors (match outcome, match location, and opponent quality) and match running performance (MRP). The dataset comprised 1806 individual observations obtained from 160 matches with 509 players from 36 participating teams across the UEFA Champions League 2024/25 season. Metrics included total distance covered (TD), low-(LIR), moderate-(MIR), and high-intensity running (HIR), high-speed running (HSR), sprinting (SPR), and high-intensity accelerations (HIAs) and decelerations (HIDs). Significant playing position × match outcome interactions were observed for TD (F = 2.75, p = 0.005), MIR (F = 2.39, p = 0.015), HIR (F = 5.24, p < 0.001), HSR (F = 3.90, p < 0.001), and SPR (F = 3.69, p < 0.001). Significant playing position × opponent quality interactions were also identified for TD (F = 8.77, p < 0.001), LIR (F = 3.56, p = 0.007), MIR (F = 6.20, p < 0.001), HSR (F = 3.09, p = 0.015), and HIDs (F = 5.14, p < 0.001). In contrast, no significant playing position × match location interactions were observed. Match outcome, match location, and opponent quality explained 0.7–2.5% of overall variability in MRP (Part R² = 0.007–0.025). Therefore, these contextual factors should be considered as supplementary information that may improve the interpretation of position-specific MRP rather than as factors that substantially determine the physical demands imposed during match-play. Full article

Butyl benzyl phthalate (BBP), a widely used endocrine-disrupting chemical, has been associated with reproductive toxicity; however, its long-term effects during aging remain poorly understood. In the present study, we examined the effects of prolonged BBP exposure on the male reproductive system using naturally aged C57BL/6J mice. Mice received BBP at 169 μg/kg/day in drinking water for 10 or 22 months and were analyzed at 24 months of age. No significant differences in body weight, food intake, or water consumption were observed among the experimental groups. Representative gross images showed apparent distension and dark-red discoloration of the seminal vesicles in BBP-exposed aged mice. Compared with Young mice, the BBP-exposed aged groups showed higher expression of IL-1β, IL-6, TNFα, SOD1, and SOD2 and lower CAT expression in the seminal vesicle. H₂DCFDA fluorescence showed a non-significant increasing trend. Because an untreated age-matched Old group was not included in the seminal vesicle analyses, the effects of aging and BBP could not be distinguished. In contrast, the testis showed limited changes in inflammatory cytokine-, antioxidant enzyme-, and steroidogenesis-related gene expression and in H₂DCFDA fluorescence relative to the untreated Old group. Exploratory miRNA sequencing of pooled testicular RNA and comparison with a TM3 Leydig cell dataset identified miR-664-5p as a candidate showing higher relative abundance in both datasets. TargetScan analysis predicted binding sites for miR-664-5p in FOXO1 and FOXO3. In BBP-treated TM3 cells, FOXO3 protein expression was decreased, and FOXO6 expression was increased, whereas FOXO1 showed no consistent dose-dependent change. These molecular findings do not establish direct regulation of FOXO proteins by miR-664-5p or explain the seminal vesicle findings. Full article

Insects periodically undergo molting to replace their old epidermis for growth and morphological adaptation. Muscleblind-like (MBNL) is a multifunctional protein involved in miRNA processing. To explore the role of miRNA processing in insect molting, we characterized BmMBNL in Bombyx mori. BmMBNL exhibited spatiotemporal expression across tissues and developmental stages, with the highest levels in the epidermis and upregulation during molting. CRISPR/Cas9-mediated knockout of BmMBNL (BmMBNL-KO) caused molting defects at the 3rd and 4th instar larvae, resulting in reduced size and eventual lethality. Moreover, BmMBNL-KO individuals showed a thinner chitin layer between the new and old epidermises. RT-PCR and transcriptome analyses revealed upregulation of miR-1, miR-71, miR-263, miR-8-5p, and miR-2a-3p, which suppressed chitinase expression, ultimately leading to molting failure. This study provides novel insights into the potential correlation between BmMBNL, miRNA abundance and insect molting in Bombyx mori. Full article

Background: Frontotemporal dementia (FTD) is a neurodegenerative disease that shares numerous clinical features with other forms of dementia. In this context, non-coding RNAs, specifically microRNAs (miRNAs), represent a promising tool for differential diagnosis. Since these miRNAs can be isolated from circulating extracellular vesicles (EVs) in peripheral blood, they provide a direct insight into FTD-specific molecular processes. Consequently, while EV-contained miRNAs hold potential as disease-specific biomarkers, investigating their relative target genes can help elucidate their precise functional roles. Aim: This work aimed to identify a specific miRNA signature to better characterize FTD pathology. Methods: Building on a previous Next-Generation Sequencing (NGS) analysis, three candidate miRNAs were selected for validation in both EVs and peripheral blood mononuclear cells (PBMCs) of FTD patients. Subsequently, the predicted target genes of two of these miRNAs were validated in PBMCs to assess their expression levels. Results: Our findings revealed that miR-365a-3p and miR-212 were significantly down-regulated in FTD. Conclusions: Together with their target genes, these miRNAs are involved in cell cycle and apoptotic pathways, suggesting a potential role in the pathological mechanisms of the disease. Full article

Background: The Investigator Quantiplex Pro RGQ Kit (Qiagen, Hilden, Germany) enables rapid quantification of total human and male DNA on the Rotor-Gene Q platform while simultaneously assessing PCR inhibition, DNA degradation, and mixed DNA profiles. This study evaluated whether reducing the recommended qPCR reaction volume by half affects analytical performance, with the aim of improving throughput and reducing reagent costs in forensic laboratories. Methods: Control DNA (50 ng/µL) and DNA extracted from 20 simulated forensic samples representing common forensic evidence (including bloodstains, semen stains, saliva samples, vaginal swabs, touch DNA, hair roots, and mixed biological traces deposited on different substrates) were analyzed using standard and half-volume qPCR reactions with identical reagent proportions. Quantification and quality indices—including inhibition (IC), degradation (DI), and mixture (MI)—were evaluated using Q-Rex software. Ct values, ΔCt, and standard deviations were compared between protocols using paired statistical analysis, with significance set at p < 0.05. Results: Standard curves generated under both reaction conditions showed efficient amplification, with R² values > 0.998 and slopes within recommended ranges. Control samples demonstrated strong agreement between expected and measured DNA concentrations for both protocols. Although forensic samples displayed variable DNA quantity and quality, highly concordant results were obtained between standard and reduced volumes. Mean Ct values showed minimal ΔCt variation and low dispersion across all sample types. IC, DI, and MI indices were also consistent, indicating reliable detection of inhibition, degradation, and mixed DNA profiles under reduced-volume conditions. Conclusions: Half-volume qPCR reactions using the Investigator Quantiplex Pro RGQ Kit maintained accurate, precise, and reproducible DNA quantification and quality assessment. Reduced-volume protocols may therefore provide a cost-effective strategy to increase throughput and improve workflow efficiency in forensic laboratories without compromising analytical robustness. Full article

Background/Objectives: Loss of phosphatase and tensin homolog (PTEN) activity is a frequent feature of non-small-cell lung cancer (NSCLC), and epigenetic repression may contribute to its reduced expression. This study investigated the effects of 5-aza-2′-deoxycytidine (5-aza-dC) on PTEN, DNA methyltransferase 1 (DNMT1), PTEN promoter methylation-specific amplification patterns, and miR-148a-3p expression in NSCLC models. Methods: Publicly available cancer-genomics datasets were analyzed to compare PTEN and DNMT1 transcript abundance and to assess the association between PTEN methylation and transcript abundance in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). A549 and H460 cells were exposed to 2.5 or 5 µM 5-aza-dC for 72 h. Reverse-transcription quantitative PCR (RT-qPCR), Western blotting, methylation-specific PCR (MSP-PCR), and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays were used to evaluate RNA expression, protein abundance, methylation-specific amplification, and metabolic activity, respectively. Results: Bioinformatic analyses showed lower PTEN and higher DNMT1 expression in both NSCLC subtypes, together with inverse associations between PTEN methylation and transcript abundance. In both cell lines, 5-aza-dC reduced MTT metabolic activity and DNMT1 expression. PTEN mRNA and protein abundance increased significantly at 5 µM, whereas no significant changes were detected at 2.5 µM. MSP-PCR revealed persistent heterogeneous PTEN methylation-specific amplification patterns without clear evidence of progressive promoter demethylation. miR-148a-3p exhibited a biphasic response in A549 cells but remained unchanged in H460 cells. Conclusions: These findings support an association between 5-aza-dC exposure, increased PTEN expression, and reduced DNMT1 expression in NSCLC cells. Quantitative methylation analysis and mechanistic validation are required to clarify the contribution of miR-148a-3p to this regulatory association. Full article

Background: Hypertrophic cardiomyopathy (HCM) is the most common monogenic cardiac disorder (prevalence 1:500), a major substrate of sudden cardiac death (SCD) in adolescents and young adults, and is modulated by regulatory mechanisms including non-coding RNAs (ncRNAs) such as microRNAs (miRNAs), long non-coding RNAS (lncRNAs) and circular RNAs (circRNAs), which act as epigenetic modulators and potential biomarkers. Methods: The study involves a PRISMA-based systematic review of 989 records from PubMed, Scopus, Embase, Web of Science and Cochrane, including 96 studies evaluating ncRNAs as diagnostic, prognostic, genotype-specific or mechanistic markers in clinically/genetically confirmed HCM. Human biomarker studies (circulating/tissue ncRNAs) were analyzed separately from experimental models (human myocardium, animal models, iPSC-derived cardiomyocytes, cardiac organoids). Results: Key findings include upregulated miR-29a, miR-21 and miR-133a in HCM plasma/tissue (correlating with hypertrophy/fibrosis), miR-499a-5p as an MYH7-specific marker, and miR-208b-3p/miR-155 associated with MYBPC3-related HCM. Pro-hypertrophic lncRNAs (e.g., NEAT1, UCA1), fibrotic lncRNAs (e.g., MIAT) and protective/mitochondrial circRNAs (e.g., circZFPM2) contribute to ceRNA networks linking hypertrophy, fibrosis, mitochondrial dysfunction and arrhythmic remodeling. Multi-ncRNA panels have shown discriminatory performance between HCM and selected phenocopies, while some signatures have been associated with atrial fibrillation and composite cardiac outcomes; however, these findings remain heterogeneous and require independent validation. Conclusions: NcRNAs are biologically relevant regulators of HCM and represent promising candidates for mechanistic investigation, biomarker development and, potentially, therapeutic targeting. Current clinical evidence remains insufficient to support their incorporation into established SCD risk prediction models or their use as standalone diagnostic tools, particularly given the heterogeneity of cohorts, sample sources and analytical approaches. Their potential forensic relevance is also exploratory: ncRNA profiling may provide an additional molecular layer for the characterization of cardiomyopathic substrates in unexplained SCD, but its specificity, post-mortem stability and incremental value over conventional autopsy, histopathology and molecular autopsy remain unestablished. Dedicated longitudinal clinical and forensic studies are required before ncRNAs can be considered for routine clinical or post-mortem application. Full article

Perirenal adipose tissue (PRAT) has emerged as a clinically relevant endocrine organ connecting obesity to cardiovascular disease (CVD), chronic kidney disease, and certain malignancies. Its unique anatomical location, surrounding the kidneys, accounts for PRAT’s role in altering intrarenal haemodynamics and hydrostatic pressure. Accordingly, PRAT’s expansion is associated with the activation of the renin–angiotensin–aldosterone system (RAAS), further increasing blood pressure. Adipokine dysregulation, together with overexpression of miR-24-3p, miR-155, miR-146a, and miR-21 in PRAT, modulates inflammation and oxidative stress, leading to endothelial dysfunction and increased risk of atherosclerosis and hypertension in obesity. Imaging assessment of PRAT thickness through computed tomography, magnetic resonance, or ultrasound has also emerged as a complementary measure for the evaluation of CVD risk. Potential therapeutic strategies targeting PRAT include lifestyle interventions, antidiabetic agents, RAAS inhibitors, adipose tissue browning agents, NOD-like receptor protein 3 (NLRP3) inflammasome inhibitors, peroxisome proliferator-activated receptor gamma (PPARγ) agonists, and surgery. Currently, novel therapeutic interventions targeting PRAT activity in CVD, such as senotherapeutic strategies, bioengineering approaches aimed at enhancing adipose-derived mesenchymal stem cell (ADMSC) function, gut microbiota modulation, and colchicine and bone morphogenetic protein 4 (BMP4) administration, are also being explored. In light of these findings, PRAT’s clinical relevance extends beyond its energy storage role, highlighting it as a metabolically active fat depot. Its assessment and therapeutic modulation may complement existing cardiovascular prevention strategies, particularly in patients with obesity. Full article

Circulating extracellular vesicle-associated microRNAs (EV-miRNAs) are emerging as promising peripheral biomarkers in multiple sclerosis (MS). This prospective, observational pilot study was conceived as a hypothesis-generating investigation to characterize the expression profile of four candidate EV-miRNAs (miR-223-5p, miR-155-5p, miR-30a-5p, and miR-146a-5p) within an EV-enriched plasma fraction. The cohort comprised 16 patients with secondary progressive MS (SPMS) undergoing siponimod therapy, 13 age- and sex-matched healthy controls (HCs), and 7 patients with relapsing–remitting MS (RRMS) included as an exploratory comparator. Quantification was performed by quantitative real-time PCR employing the ΔΔC_t methodology, with miR-16-5p as the endogenous normalizer. Analyses were conducted cross-sectionally and longitudinally, the latter within a paired subgroup of 11 SPMS patients evaluated at baseline and after twelve months of uninterrupted treatment. Cross-sectional comparisons demonstrated a significant downregulation of EV-miR-223-5p in SPMS patients relative to HCs (fold-change [FC] = 0.26; FDR q = 0.026), whereas EV-miR-155-5p was significantly reduced in both the SPMS (FC = 0.35; FDR q = 0.033) and RRMS (FC = 0.28; FDR q = 0.046) cohorts compared with HCs. No significant intergroup differences were observed for EV-miR-30a-5p or EV-miR-146a-5p. Longitudinal assessment revealed no significant modulation of any target EV-miRNA following one year of siponimod therapy. These preliminary observations should be interpreted with caution, given the exploratory nature and modest cohort size. Importantly, the isolation of total plasma EVs does not permit resolution of the specific cellular provenance of the observed signals, nor does it capture their downstream functional consequences. Nevertheless, the selective downregulation of EV-miR-223-5p and EV-miR-155-5p may tentatively suggest candidate molecular signatures warranting further interrogation. Adequately powered studies incorporating cell-specific EV sorting and paired cerebrospinal fluid sampling will be required to substantiate these signals and clarify their potential utility in monitoring disease progression and therapeutic response in progressive MS. Full article

Background: Autophagy is a process that diversely impacts the stages of both tumor initiation and progression. Elucidating the molecular mechanisms underlying autophagy and its role in tumorigenesis is a key component of anticancer strategies in both prostate cancer and other malignancies. Because advanced prostate cancer frequently exploits enhanced autophagy as a defense mechanism against therapy-induced stress (e.g., from abiraterone), the pharmacological modulation of miRNA levels presents a tremendous opportunity to block the tumor’s escape route and overcome drug resistance. Methods: A comprehensive literature review was conducted to evaluate the molecular pathways determining cancer cell survival and death. The analysis focused on the dual nature of autophagy (functioning as a ‘double-edged sword’) within the tumor microenvironment, microRNA (miRNA) regulatory networks, and the efficacy of synergistic therapeutic strategies in overcoming treatment resistance. Results: The primary focus of this paper is the dual and complex role of autophagy, which serves, on the one hand, as a cellular protective shield against metabolic stress—thereby facilitating metastasis—and, on the other hand, as a potential pathway leading to autophagic cell death. The progression of this crucial process is regulated by intricate interactions (crosstalk) with apoptotic pathways, mediated by Bcl-2 family proteins, key kinases (such as mTOR, JNK, and DAPK), and transcription factors, such as p53. Furthermore, the autophagic machinery is precisely regulated by specific miRNA molecules (e.g., miR-21, miR-141, and miR-375). These not only act as crucial intracellular modulators of autophagy but also serve as promising circulating biomarkers, enabling the monitoring of this process’s activity throughout disease progression. Conclusions: Autophagy, and in particular its modulation via miRNA signaling networks, represents a major and highly promising translational target. By directly impairing this autophagic survival mechanism, ‘double-hit’ combination therapies—integrating autophagy inhibitors (such as hydroxychloroquine or VPS34 inhibitors) with standard antiandrogen or cytotoxic agents—demonstrate promising preclinical potential in overcoming treatment resistance and favorably modulating the immune microenvironment in advanced prostate cancer. Full article

Endometriosis affects approximately 10% of women of reproductive age and is associated with infertility in up to half of those diagnosed. Despite decades of research, the molecular basis of its reproductive consequences remains poorly defined. Among the pathophysiological features most consistently documented in affected women, chronic oxidative stress within the peritoneal cavity has attracted sustained attention, yet its relationship to the extracellular vesicle biology that has emerged as central to endometriosis pathogenesis has never been systematically examined. Iron-catalyzed radical chemistry, macrophage-derived superoxide, and mitochondrial electron leak in ectopic stromal cells collectively sustain a peritoneal redox burden that modifies exosomal biogenesis, alters microRNA sorting, and reprograms vesicle lipid and protein cargo. Oxidatively conditioned exosomes skew peritoneal macrophages toward an immunosuppressive M2 phenotype through miR-301a-3p, miR-146a-5p, and miR-196a-5p, suppress natural killer cell cytotoxicity through NKG2D ligand decoy delivery, facilitate peritoneal dissemination and neuroangiogenesis, and compromise oocyte developmental competence through ferroptosis-derived vesicles carrying aberrant miR-122-5p, oxidized phosphatidylethanolamines, and damaged mitochondria. These mechanisms map directly onto the clinical deficits observed in women with endometriosis undergoing assisted reproduction, including reduced oocyte yield, lower fertilization rates, elevated embryo aneuploidy, and impaired implantation. Follicular and peritoneal fluid exosomal microRNA profiles represent promising non-invasive biomarkers, while combinatorial strategies targeting the iron-ROS-exosome axis offer a more coherent therapeutic framework than the single-antioxidant approaches that have so far shown limited benefit. Full article

Alterations in body composition are clinically relevant features occurring in patients with breast cancer (BC), but the mechanism remains poorly defined. We investigated whether circulating microRNAs (miRNAs) involved in skeletal muscle (SM) and adipose tissue (AT) metabolism are associated with body composition alterations in BC. We analyzed by RT-qPCR circulating levels of SM- and AT-related miRNAs in a cohort of breast cancer patients (BCPs) (n = 46) and controls (n = 16). Associations between miRNA profiles and body composition parameters were evaluated. miR-21, miR-29a, and miR-29b were upregulated in BCPs compared with controls (all p < 0.05). miR-133a was downregulated in patients with low muscle mass (p = 0.040), independently of adiposity. miR-133a was found to be lower in BCP subgroups with LUM-B and low levels of muscularity compared to those with LUM-A or LUM-B with high muscularity levels (all p < 0.05). Correlation analyses supported a closer association of miR-133a with SM-related parameters than with fat mass. miR-21, miR-29a and miR-29b appeared to reflect tumor-related systemic signaling. miR-133a was associated with reduced SM mass and influenced by tumor molecular subtype. These results suggest that miR-133a might represent a potential mediator of cancer-associated SM alterations and warrant validation in larger longitudinal studies. Full article