Search Results (4,653)

Zinc oxide nanoparticles (ZnO NPs) are widely used in biomedical, agricultural, and industrial applications, raising concerns about their potential hepatotoxicity. This study investigated the effects of 28-day oral ZnO NP exposure on hepatic function, oxidative stress, apoptosis, inflammatory signaling, and microRNA expression in rats. Sixty male Wistar albino rats were allocated to three groups (n = 20 each),control, low dose (30 mg/kg), and high dose (100 mg/kg), and treated by oral gavage. The administered material had a nominal particle size of 50 nm and a supplier-stated purity of 99.9%. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), hepatic malondialdehyde (MDA) and reduced glutathione (GSH), histopathology, immunohistochemistry, mRNA expression, and hepatic microRNAs were assessed. ZnO NPs induced dose-related liver injury: ALT increased from 31.26 ± 2.5 to 75.48 ± 12.3 IU/L, while AST increased from 32.47 ± 4.1 to 85.57 ± 18.9 IU/L. Hepatic MDA increased, whereas GSH increased at the low dose but was depleted at the high dose. Histopathology demonstrated sinusoidal congestion, hepatocellular necrosis, and inflammatory infiltration. Immunohistochemistry indicated reduced B-cell lymphoma 2 (Bcl-2) and increased caspase-3 and tumor necrosis factor-alpha (TNF-α) immunoreactivity. Interleukin-6 (IL-6) and heme oxygenase-1 (HO-1) were upregulated, whereas superoxide dismutase 2 (SOD2) was downregulated. At the high dose, miR-122-5p, miR-34a-5p, and miR-21-5p increased by 8.74-, 6.53-, and 4.38-fold, respectively (all p< 0.05). Their expression levels were also strongly and positively correlated with biochemical, oxidative, and histopathological indicators of liver injury. These findings indicate that ZnO NP exposure is associated with oxidative, inflammatory, apoptotic, and microRNA responses; the altered hepatic microRNAs may represent candidate tissue indicators of ZnO NP-induced liver injury. Full article

Background: The discovery of non-invasive biomarkers that can predict the therapeutic response in Inflammatory Bowel Disease (IBD) is of utmost importance in the field of personalized medicine. The present prospective cohort study was designed to investigate the use of circulating levels of plasma microRNA-145 (miR-145) and microRNA-191 (miR-191) in the diagnosis and association with therapeutic response in Crohn’s disease (CD) and ulcerative colitis (UC). Methods: The present study was conducted as a retrospective observational cohort study on 183 adult IBD patients, consisting of 96 CD patients and 87 UC patients. Patient data and study parameters were obtained retrospectively from existing clinical records and available laboratory/molecular data collected during routine clinical care. A healthy control group consisting of 92 individuals was included for comparison with the patients with IBD. The circulating levels of miR-145 and miR-191 were assessed in the peripheral blood plasma at baseline using qRT PCR. The clinical response was evaluated at 12 weeks using the CDAI score for CD and the Mayo score for UC. Results: In active IBD, there was significant down-regulation of miR-145 and significant up-regulation of miR-191. Responders at 12 weeks had significantly higher levels of baseline miR-145 (2.0-fold, p < 0.001) and lower levels of miR-191 (1.8-fold, p < 0.001) compared with non-responders. Also, miR-145 negatively correlated with disease activity, and miR-191 positively correlated with acute inflammation markers. ROC curve analysis showed good discriminative values for both miR-145 and miR-191. Conclusions: The level of circulating miR-145 and miR-191 correlates with the activity of IBD. Importantly, the baseline level of miR-145 expression is a non-invasive potential biomarker associated with therapeutic response at 12 weeks. Full article

To investigate microRNA-369-5p (miR-369-5p) and miR-671-3p expression in maternal peripheral blood leukocytes, plasma, and placental tissue in women with intrahepatic cholestasis of pregnancy (ICP) undergoing intracytoplasmic sperm injection (ICSI), compared with spontaneous conception. In this exploratory cohort study, microRNA-369-5p (miR-369-5p) and microRNA-671-3p (miR-671-3p) expression levels were analyzed using real-time quantitative PCR in maternal peripheral blood leukocytes, plasma, and placental tissue in four groups: (1) women with uncomplicated pregnancies conceived via intracytoplasmic sperm injection (non-ICP-ICSI, n = 7), (2) women with intrahepatic cholestasis of pregnancy conceived via intracytoplasmic sperm injection (ICP-ICSI, n = 7), (3) women with intrahepatic cholestasis of pregnancy who conceived spontaneously (ICP-SC, n = 7), and (4) women with uncomplicated pregnancies conceived spontaneously (non-ICP-SC, n = 7). Relative expression levels were calculated using the RQ method. Leukocyte miR-369-5p expression was significantly upregulated in ICP-ICSI and non-ICP-ICSI groups compared with ICP-SC and non-ICP-SC groups (p = 0.0001). Plasma miR-671-3p expression levels were significantly decreased in ICSI groups compared with spontaneous conception groups (p = 0.029). No significant differences were observed in placental expression levels of miR-369-5p and miR-671-3p among the four groups (p > 0.05). In subgroup analysis, leukocyte miR-369-5p and miR-671-3p expression levels were significantly higher in the ICP-ICSI group compared with the ICP-SC group (p < 0.05). Serum fasting bile acid levels showed a significant positive correlation with placental miR-369-5p expression (r = 0.467; p = 0.012) and a negative correlation with plasma miR-369-5p expression (r = −0.413; p = 0.029). Our findings show compartment-specific differences in miR-369-5p and miR-671-3p expression across leukocytes and plasma in this exploratory cohort. These preliminary observations do not establish causality and require validation in larger, independent cohorts. Full article

Background/Objectives: Chronic lymphocytic leukemia (CLL) is characterized by marked clinical heterogeneity, underscoring the need for reliable biomarkers to improve diagnosis and risk stratification. Extracellular vesicles (EVs) represent promising liquid biopsy candidates because they reflect the molecular profile of their cells of origin. In CLL, CD200 is a well-established marker of tumor cells; its expression on EVs and its role as a CLL biomarker were poorly characterized. This study investigated the diagnostic and prognostic value of serum EVs in CLL. Methods: Serum EVs were isolated from 83 patients with CLL and 20 healthy subjects (HS). EV morphology, size, and concentration were assessed by transmission electron microscopy and nanoparticle tracking analysis. Flow cytometry was used to evaluate the expression of CD19, CD20, and CD200 on EVs, while digital PCR quantified EV-associated miR-93-5p, miR-125b-5p, miR-150-5p, and miR-484. Results: Compared with HS, CLL patients showed increased total EV counts and higher levels of CD19⁺, CD20⁺, CD200⁺, and CD19⁺/CD20⁺ EVs, together with enhanced CD20 and CD200 expression and reduced miR-93-5p, miR-125b-5p, and miR-484 levels. In contrast, EV-associated miR-150-5p levels were comparable between CLL patients and HS. EV features were correlated with clinical and biological characteristics, including disease stage, cytogenetic abnormalities, treatment, and time to treatment (TTT). Older age was associated with lower EV concentrations but higher CD20 and CD200 expression. Advanced-stage disease was characterized by smaller EVs with increased CD200 expression. Notably, elevated CD200⁺ EV levels and reduced CD19 expression were associated with shorter TTT and earlier treatment initiation. Conclusions: Multiparametric profiling identified distinct quantitative, phenotypic, and molecular features of CLL-derived EVs and revealed CD200 as a novel EV-associated biomarker. These findings support the clinical utility of serum EVs as a new valuable approach for CLL diagnosis, prognosis, and treatment prediction. Full article

Background/Objectives: Repurposing existing drugs may represent a promising strategy for effective cancer therapy. This study was the first to investigate the augmented antitumor therapeutic effect achieved by co-incorporating the NSAID Niflumic acid (NIF) with ceramides into PEGylated cerosomes (NIF-loaded PEG-CERs) in a novel platform that targets specifically the MAPK-ERK signaling pathway and miR-21-5p modulation. Methods: The prepared formulae were statistically optimized utilizing a full factorial design and the optimal formula (C5) was further incorporated into a topical gel and evaluated for ex vivo rat skin permeation, and tested in vivo in a subcutaneous solid Ehrlich carcinoma (SEC) mice model. Results: The optimal formula (C5) showed tubular elongated morphology with higher EE% (96.71 ± 0.0), lower vesicular size (VS) and PDI values, 292.95 ± 0.78 nm and 0.47 ± 0.0 respectively. A high ZP value (−37.5 ± 0.57 mV) was in accordance with stability results showing good stability of the optimal formula (C5). Permeability studies exhibited 2.02-fold higher skin permeation compared to pure NIF gel. A significant decrease in tumor volume and marked improvement in survival rate in SEC mice were confirmed by downregulation of EGFR, ERK1, ERK2, and miR-21-5p expression. Furthermore, an increase in total antioxidant capacity and caspase-3 levels was observed, accompanied by significant suppression in cyclin D1, MMP-2, COX-2, and MDA levels. Finally, histopathological analysis revealed the superior antitumor effect of C5 gel together with immunohistochemical assay showing the lowest BCL-2-positive staining, indicating the restoration of physiological apoptotic balance. Conclusions: Based on the previous findings, NIF-loaded PEG-CERs offer augmented therapeutic potential for efficient topical skin cancer management in an SEC mice model. Full article

Patients with early-stage myocardial infarction (MI) are at high risk of malignant ventricular arrhythmias, yet the cell-type-specific molecular landscape associated with post-infarction arrhythmogenesis has not been systematically characterized. This study integrates single-nucleus and spatial transcriptomics to define a cardiomyocyte subpopulation in early MI and dissect the NEAT1-centered regulatory network driving its ion channel remodeling. Single-nucleus transcriptomic data from post-MI human hearts were re-analyzed to identify a distinct subpopulation, termed arrhythmia-potential cardiomyocytes (aCMs), within the infarct border zone, characterized by pronounced ion channel remodeling. Gene co-expression network analysis revealed two modules highly associated with aCMs, in which NEAT1 correlated with the calcium channel gene CACNA1C and the LIM domain protein PDLIM5. All three genes were upregulated in hypoxic rat cardiomyocytes; siRNA-mediated knockdown confirmed that NEAT1 silencing downregulated CACNA1C and PDLIM5 expression, consistent with in silico knockout predictions. A ceRNA network further identified hsa-miR-204-5p/211-5p as a key mediator consistent with regulatory axis. These findings suggest that cardiomyocytes in the early MI border zone exhibit ion channel remodeling driven by elevated NEAT1, which may modulate CACNA1C and PDLIM5 through a microRNA-mediated ceRNA network, suggesting that targeting NEAT1 may warrant further investigation for preventing malignant arrhythmias in early-stage MI. Full article

Background/Objectives: Extracellular vesicles (EVs) have emerged as important mediators of intercellular communication in cardiovascular disease, particularly through the transfer of regulatory microRNAs. However, direct evidence of cytosolic microRNA delivery by mesenchymal stem cell (MSC)-derived EVs into cardiomyocytes remains limited. Many prior studies have inferred transfer without fully excluding endogenous microRNA induction or surface-bound artifacts. The objective of this study was to determine whether MSC-derived EV microRNA undergoes functional cytoplasmic delivery into cardiomyocytes and to identify the endocytic pathways involved. Methods: To eliminate background from endogenous microRNA expression, MSC-derived EVs were loaded with the exogenous microRNA cel-miR-39-3p. H9C2 cardiomyocytes were treated with increasing vesicle doses, and intracellular microRNA levels were quantified using real-time polymerase chain reactions. Cytosolic accessibility was assessed indirectly using a cholesterol-modified antagomir targeting cel-miR-39-3p. Pharmacologic inhibitors of macropinocytosis (5-(N-ethyl-N-isopropyl) amiloride (EIPA)) and clathrin-mediated endocytosis (chlorpromazine and ES9-17) were applied to delineate uptake pathways, with transferrin assays confirming clathrin inhibition. Results: EV treatment produced a dose-dependent increase in intracellular cel-miR-39-3p levels. Antagomir administration reduced intracellular microRNA levels by 89%, providing indirect functional evidence that transferred cel-miR-39-3p reached an antagomir-accessible cytosolic compartment. At the highest preparation dose, EIPA and ES9-17 reduced cell-associated cel-miR-39-3p by 71% and 36%, respectively, consistent with contributions from EIPA-sensitive and clathrin-associated uptake processes. Notably, chlorpromazine increased microRNA accumulation despite blocking transferrin uptake, suggesting compensatory or membrane curvature-dependent effects. Conclusions: These findings provide strong functional evidence that exogenous cel-miR-39-3p associated with MSC EV preparations reaches an antagomir-accessible cytoplasmic compartment in H9C2 cardiomyocytes and implicate EIPA-sensitive uptake consistent with macropinocytosis and clathrin-associated uptake. Additional genetic, localization, and pulse-chase studies are required to establish the precise intracellular trafficking mechanisms. This work strengthens the mechanistic foundation for EV-based therapies and informs the rational development of cell-free strategies for cardiovascular disease. Full article

α-Amylases are involved in starch breakdown, thereby influencing plant development. Information on the α-amylase genes in soybean is limited. Here, we identified five soybean α-amylase genes from subfamilies AtAMY1 (GmaAMY5), AtAMY2 (GmaAMY4), AtAMY3 (GmaAMY1, GmaAMY3), and AMY6 (GmaAMY2). In silico analysis indicated that all five genes were actively expressed in leaves, flowers, and pods but weakly in roots. GmaAMY1–GmaAMY5 mRNAs were predicted to be targets of miRNAs associated with stress response, organ development, and nitrogen fixation. Putative GmaAMY1–GmaAMY5 proteins contained α-amylase-specific catalytic domain, signatures, and active sites. Short-term abiotic stresses (100 mM NaCl, 2.5–20% PEG, and 4 °C cold) applied to the cv. Doka affected both GmaAMY1–GmaAMY5 expression and the content of starch and soluble sugars in leaves. GmaAMY1 gene expression increased in response to NaCl and PEG, GmaAMY2 in response to PEG, and GmaAMY5 in response to NaCl. Salt stress suppressed the expression of the GmaAMY2–GmaAMY4 genes. The mRNA levels of all five genes increased after 2 h of cold exposure. Under salinity stress, there was inverse correlation of starch content with GmaAMY4 expression (r = −0.5135, p = 0.0293) and overall GmaAMY1–GmaAMY5 expression (r = −0.6318, p = 0.0049), suggesting a possible role of GmaAMY genes in protecting soybean from salinity by maintaining the starch/soluble sugars balance. Our results may aid in the breeding of stress-tolerant soybean varieties. Full article

Background: Endometriosis-associated ovarian cancers (EAOCs), including ovarian clear cell (OCCC) and endometrioid ovarian carcinoma (EnOC) subtypes, frequently exhibit transcriptomic dysregulation of the PI3K/AKT/mTOR signalling axis. While genomic aberrations are well-documented, the coordinated microRNA (miRNA)-mediated networks governing post-transcriptional remodelling of this pathway across these subtypes remain poorly defined. Methods: We conducted an integrative in silico meta-analysis of independent mRNA and small RNA sequencing datasets. The mRNA analysis included 120 EAOC samples, of which 68 were OCCC and 52 were EnOC, compared with 149 normal ovarian tissues. The miRNA analysis included 170 samples comprising 55 OCCC, 82 EnOC and 33 normal ovarian tissues. Differential expression analysis, dimensionality reduction (UMAP), functional enrichment, and topologically unweighted miRNA–mRNA interaction networks were evaluated. Results: Both subtypes showed significant transcriptomic dysregulation of the core pathway machinery, including PIK3CB and mTOR, while preserving mTORC2 components. Post-transcriptional concurrent downregulation of IRS1, GRB10, DDIT4, and PIK3CD, which were identified as candidate targets of the hub miRNAs hsa-miR-30a-5p, hsa-miR-30d-5p, and hsa-miR-7-5p, suggests further refined control of the pathway. The identification of highly connected hub genes linking mTOR, MAPK, and Wnt signalling pathways within the mTOR-regulatory network suggests that pathway modulation occurs through extensive crosstalk across multiple oncogenic signalling pathways in EAOCs. Conclusions: Transcriptomic dysregulation of the mTOR pathway in EAOCs reflects not only genomic alterations but also potential post-transcriptional regulation. Despite subtype-specific transcriptomic differences, both exhibited transcriptional upregulation of components of the canonical PI3K/AKT/mTOR signalling axis. Pathway modulation through the miRNA regulatory network exhibited potential crosstalk across oncogenic pathways and hub genes. Full article

Progressive resistance exercise training (RET) enhances skeletal muscle mass in healthy postmenopausal women (HEAs) and breast cancer survivors (BCSs) undergoing endocrine therapy. MicroRNAs (miRNAs) are recognized as key epigenetic regulators of exercise-induced adaptations, functioning as tumor suppressors, oncomiRs, and modulators of skeletal muscle homeostasis. Nevertheless, the impact of RET on circulating miRNA profiles in this population remains largely unexplored. This study aimed to explore the effects of a 12-week progressive RET program on plasma miRNAs associated with tumor biology and skeletal muscle regulation in HEAs and BCSs. Five HEAs and five BCSs undergoing endocrine therapy completed a 12-week supervised progressive RET program (3 sessions/week, 60–80% 1RM). Plasma samples were collected before and after intervention, and candidate miRNA expression was quantified by qRT-PCR, normalized to hsa-miR-16-5p, and analyzed using the 2^−ΔΔCt method. At baseline, no significant differences were observed between HEA and BCS in tumor suppressor miRNAs (miR-let-7f-5p, miR-125a-5p, miR-342-3p), oncomiRs (miR-21-5p, miR-155-5p, miR-221-3p), or skeletal muscle–related miRNAs (miR-206-3p, miR-486-5p) (p > 0.05). The only exception was miR-375-3p, which showed increased expression in HEA vs BCS (p = 0.037). After 12 weeks of RET, The BCS group showed increases in miR-125a-5p (p = 0.050) and miR-342-3p (p = 0.048) with significant group × time interactions that remained significant after Benjamini–Hochberg False Discovery Rate (BH-FDR) correction (FDR-adjusted p = 0.042 for both). Both groups displayed a nominal increase in miR-375-3p (p = 0.042), which did not remain significant after FDR correction. No significant changes were detected for miR-let-7f-5p or the analyzed oncomiRs in either group. Both miR-206-3p and miR-486-5p exhibited upward trends in the BCS group (p > 0.05). In this exploratory study, 12-week RET program was associated with selective changes in plasma miRNA expression in the HEA and BCS groups, suggesting that this training regimen may act as an epigenetic modulator of circulating miRNAs involved in tumor suppression and skeletal muscle homeostasis. Full article

Background/Objectives: OS is characterized by marked tumor heterogeneity, stemness-associated phenotypes, metastatic potential, and poor prognosis. FZD4 is an important Wnt signaling receptor involved in stem cell regulation and tumor progression, but its role and microRNA-mediated regulation in OS remain unclear. The aim of this study was to investigate the relationship between FZD4 expression, OS stemness, malignant progression, and upstream microRNA regulation. Methods:Human OS single-cell RNA sequencing data were analyzed using Seurat, CytoTRACE, and Monocle2. Tumor cell subpopulations, developmental potential, and pseudotime trajectories were evaluated. Functional enrichment analyses were performed to identify pathways associated with high FZD4 expression. MicroRNA–mRNA interaction analysis was used to predict upstream regulatory microRNAs, and immunohistochemistry, Western blotting, and in vitro and in vivo experiments were performed for validation. Results: FZD4 was mainly enriched in OS tumor cell subpopulations and was significantly associated with poor prognosis. Tumor cells with high FZD4 expression showed increased developmental potential, stemness features, and enrichment in early developmental states. Functional enrichment analysis indicated activation of epithelial–mesenchymal transition, angiogenesis, inflammatory response, KRAS signaling, hypoxia, glycolysis, and Wnt-related pathways. Clinical validation confirmed elevated expression of FZD4, OCT4, and SOX2 in OS tissues. FZD4 knockdown inhibited OS cell stem-like phenotypes and malignant behaviors, proliferation, and migration, while miR-424-5p suppressed these malignant phenotypes by targeting FZD4. Importantly, rescue experiments demonstrated that restoration of FZD4 substantially reversed the inhibitory effects of miR-424-5p mimics on sphere formation, migration/invasion, proliferation, and stemness-associated cell populations. Conclusions: Our findings identify miR-424-5p as an upstream suppressor of FZD4 and demonstrate that the miR-424-5p/FZD4 axis regulates stem-like and malignant phenotypes of OS cells, at least partly through Wnt/β-catenin signaling. This axis may represent a potential therapeutic target for OS. Full article

Background/Objectives: MicroRNAs released into spent culture medium (SCM) may reflect embryo developmental status, but their relationship with blastocyst morphology and time-lapse morphokinetic behavior remains incompletely understood. This prospective study aimed to investigate whether selected SCM microRNAs are associated with blastocyst morphological grade and early morphokinetic dynamics in human embryos. Methods: A total of 432 SCM samples were collected from embryos cultured in a time-lapse incubation system between October 2018 and July 2020. Blastocysts were classified as good, fair, or poor quality according to morphological grading. The expression levels of six candidate microRNAs, including miR-182-5p, miR-302a-3p, miR-372-3p, miR-373-3p, miR-518a-3p, and miR-519d-3p, were quantified using real-time quantitative polymerase chain reaction. Associations between microRNA expression, embryo morphology, and morphokinetic parameters were analyzed using GEE, multivariate logistic regression, and receiver operating characteristic (ROC) analysis. Results: After accounting for within-patient clustering using GEE, good-quality embryos showed significantly lower expression of miR-372-3p and miR-373-3p than poor-quality embryos. On multivariate logistic regression, lower miR-372-3p expression remained independently associated with optimal t5–t2 interval after adjustment, whereas its associations with optimal CC3 and the combined outcomes were attenuated. ROC analysis demonstrated modest discriminatory ability for miR-372-3p alone (AUC = 0.644), whereas embryo morphology alone achieved an AUC of 0.731, and the combined model incorporating morphology and miR-372-3p reached the highest AUC of 0.752. Conclusions: These findings suggest that SCM microRNA expression is associated with embryo development. In particular, reduced miR-372-3p expression may reflect more favorable blastocyst morphology and early developmental dynamics, supporting its potential as an adjunctive molecular indicator of embryo quality. Further validation incorporating embryo ploidy status and clinical outcomes is warranted before clinical application. Full article

Long intergenic non-coding RNAs (lincRNAs) are key epigenetic regulators of genome function, yet their evolutionary dynamics following whole-genome duplication (WGD) events remain poorly understood. Salmonids, which underwent a lineage-specific autotetraploidization (salmonid-specific WGD, ~88–100 million years ago), provide an excellent model to investigate the retention, divergence, and functional potential of recently duplicated non-coding elements. LincRNA repertoires were compared across five genome-annotated salmonids (Oncorhynchus tshawytscha, O. kisutch, O. mykiss, Salmo salar, and S. trutta) and their closest non-duplicated relative, northern pike (Esox lucius). LincRNAs represented ~5–7% of annotated genes in all salmonids except S. salar (18%). Sequence conservation was low relative to coding genes, with only 11–68 highly similar (e-value < 1 × 10⁻³⁰; similarity > 70% and alignments > 100 nucleotides) putative orthologues shared between salmonids and northern pike, and 161–338 among salmonids alone. Synteny conservation was modest in lincRNAs, with lower conservation in putative orthologues (8–16%) compared to putative ohnologues (8–33%). Secondary structure conservation was associated with sequence similarity (ρ = −0.45; p = 2.2 × 10⁻¹⁶), and the association was stronger among WGD ohnologues than orthologues. In S. salar and O. mykiss, lincRNA putative ohnologues showed weaker expression correlations than coding genes, suggesting widespread regulatory divergence, possibly through neo- and subfunctionalisation. Conserved salmonid lincRNAs showed enriched predicted interactions with miRNAs involved in tumour suppression, brain, bone, and muscle development (e.g., miR-455, miR-365, miR124, miR-133a, miR-140, and miR-9), a finding supported by limited transcriptomic data. Although salmonid WGD expanded lincRNA repertoires, lincRNAs have undergone rapid sequence and transcriptional divergence, with limited conservation across species based on sequence similarity, chromosomal position, synteny, and secondary structure. A subset of conserved lincRNAs retains structural features and regulatory signatures consistent with roles as miRNA sponges in brain, skeletal, and muscle development and tumour suppression, potentially acting within conserved regulatory networks. These findings provide new insights into lincRNA evolution following genome duplication and highlight the need for experimental validation of their regulatory functions. Full article

Lung cancer carries a high mortality burden, with metastatic dissemination accounting for much of its poor prognosis. Bone sialoprotein (BSP), a matricellular protein belonging to the SIBLING family, has been associated with tumor invasion; nonetheless, its role in lung cancer remains inadequately characterized. Clinical database analysis indicates that BSP is the most critical SIBLING protein associated with lung cancer proliferation and metastasis. Our clinical data also confirmed that BSP levels are higher in metastatic lung cancer compared to non-metastatic cases. We further demonstrate that BSP promotes lung cancer progression and motility through upregulated ADAM9 expression. Mechanistically, we revealed that BSP enhances ADAM9-dependent proliferation and motility via the FAK pathway. In addition, the hsa_circ_0084050/miR-373-3p regulatory axis contributes to BSP-mediated ADAM9 regulation. In an exploratory mouse metastasis model established by caudal artery injection of A549 control or stable BSP-shRNA cells into male BALB/c nude mice, BSP knockdown was associated with a lower metastatic tumor burden. Therefore, BSP may serve as a therapeutic target for limiting lung cancer progression and metastatic dissemination. Full article

Background/Objectives: This study aimed to identify a characteristic miRNA expression profile in the CSF of patients diagnosed with vestibular schwannoma and evaluate its potential for tumor assessment. Methods: In this prospective study, 17 CSF and corresponding tumor samples (seven small tumors—SVS and 10 large tumors—LVS) were collected from patients operated on for VS in a Tertiary Academic Center. The miRNA expression was analyzed using high-throughput RNA sequencing (NovaSeq 6000 Illumina). Data were normalized, and a comparative analysis of miRNA expression rankings was performed between VS patients and a public healthy donor dataset. Functional implications were explored using KEGG pathway enrichment analysis. Results: A total of 1633 miRNAs were identified in all CSF samples derived from VS patients. Comparison with healthy donors revealed a moderate ranking correlation (ρ = 0.39), with significant shifts for specific molecules like hsa-miR-766-3p and hsa-miR-182-5p. Only six miRNAs were found to correlate between CSF and tumor tissue, while 16 exhibited a negative correlation. No statistical correlation was found between tumor size and the CSF miRNA profile. KEGG analysis highlighted enriched pathways, including neurotrophin signaling and focal adhesion. Conclusions: The results of our study support the feasibility of miRNA-based CSF liquid biopsy for VS assessment. However, the results of miRNA expression profiling conducted in tumor tissue cannot be directly transferred into CSF sample analyses. Further studies are warranted to explain this phenomenon and to search for reliable miRNA markers of VS progression in the CSF liquid biopsy specimens. Full article