Search Results (299)

Background: Optical genome mapping (OGM) detects genome-wide structural variants (SVs), including balanced rearrangements and complex copy-number alterations beyond standard-of-care cytogenomic assays. In chronic lymphocytic leukemia (CLL), cytogenetic and genomic risk stratification is traditionally based on fluorescence in situ hybridization (FISH), karyotyping, targeted next-generation sequencing (NGS), and immunogenetic assessment of immunoglobulin heavy chain variable region (IGHV) somatic hypermutation status, each of which interrogates only a limited aspect of disease biology. Methods: We retrospectively evaluated fifty patients with CLL using OGM and integrated these findings with cytogenomics, targeted NGS, IGHV mutational status, and clinical time-to-first-treatment (TTFT) data. Structural variants were detected using OGM and pathogenic NGS variants were derived from a clinical heme malignancy panel. Clinical outcomes were extracted from the electronic medical record. Results: OGM identified reportable structural variants in 82% (41/50) of cases. The most frequent abnormality was del(13q), observed in 29/50 (58%) and comprising 73% (29/40) of all OGM-detected deletions with pathologic significance. Among these, 12/29 (42%) represented large RB1-spanning deletions, while 17/29 (58%) were focal deletions restricted to the miR15a/miR16-1 minimal region, mapping to the non-coding host gene DLEU2. Co-occurrence of adverse lesions, including deletion 11q/ATM, BIRC3 loss, trisomy 12, and deletion 17p/TP53, were recurrent and strongly associated with shorter TTFT. OGM also uncovered multiple cryptic rearrangements involving chromosomal loci that are not represented in the canonical CLL FISH probe panel, including IGL::CCND1, IGH::BCL2, IGH::BCL11A, IGH::BCL3, and multi-chromosomal copy-number complexity. IGHV data were available in 37/50 (74%) of patients; IGHV-unmutated status frequently co-segregated with OGM-defined high-risk profiles (del(11q), del(17p), trisomy 12 with secondary hits, and complex genomes whereas mutated IGHV predominated in OGM-negative or structurally simple del(13q) cases and aligned with indolent TTFT. Integration of OGM with NGS further improved genomic risk classification, particularly in cases with discordant or inconclusive routine testing. Conclusions: OGM provides a comprehensive, genome-wide view of structural variation in CLL, resolving deletion architecture, identifying cryptic translocations, and defining complex multi-hit genomic profiles that tracked closely with clinical behavior. Combining OGM and NGS analysis refined risk stratification beyond standard FISH panels and supports more precise, individualized management strategies in CLL. Prospective studies are warranted to evaluate the clinical utility of OGM-guided genomic profiling in contemporary treatment paradigms. Full article

Cosmeceutical peptides (CPs), which modulate various biological activities, including skin regeneration and wound healing, have emerged as promising agents in skincare. In this study, we investigated the regenerative and wound healing potential of a short peptide, CP-02 (sequence CDARSDAR), using human dermal fibroblast cells (HDFs) in vitro and a zebrafish model in vivo. In HDFs, CP-02 treatment at concentrations of 50, 100, and 200 µg/mL significantly accelerated wound closure in a dose-dependent manner (p < 0.05) and upregulated the mRNA expression of CCND1, MYC, FGF2, EFG, and IL-8 at 12 h post-treatment. In amputated zebrafish larvae, exposure to CP-02 (5 µg/mL) for 72 h significantly increased fin regeneration, with a fin area of 3.5 mm² and fin-fold length of 0.2 mm, compared with those in controls (2 mm² and 0.07 mm, respectively). Intramuscular administration of CP-02 significantly improved the healing rates in wounded adult zebrafish to 58% and 76% on 12 and 16 days post wounding (dpw), respectively, compared with the vehicle (35% and 44%, respectively). Histological analysis (H&E staining) revealed reduced inflammatory cell infiltration, complete granulation, and re-epithelialization in the CP-02-treated tissues at 12 dpw. Furthermore, mRNA expression levels of tnf-α, il-1β, tgfb1, mmp9, mmp13, and timp2b were elevated in the CP-02 group at 4 dpw, whereas those of pro-fibrotic mediators, including acta2, ctgfb, cdh1, and col9a3 reduced in muscle tissue on 12 dpw. Collectively these findings demonstrate that CP-02 promotes effective, scar-reducing regeneration and wound healing, highlighting its strong potential as a therapeutic peptide for future skincare and cosmeceutical applications. Full article

Background/Objectives: Targeted gene sequencing (TGS) for Comprehensive Genomic Profiling (CGP) use in sarcomas has recently increased in clinical practice. We report on TGS real-world data over a period of 3 years (2022–2025) at the IRCCS Istituto Ortopedico Rizzoli, with the aim of identifying potential actionable targets and providing therapeutic indications for advanced sarcoma patients. Methods: We analyzed 22 advanced sarcoma patients by using the VariantPlex Pan Solid Tumor kit panel, including 185 genes. In nine cases, saliva samples for germinal DNA analysis were available. Sequencing was performed on the NextSeq-500 Platform and analyzed with Archer Analysis software. The Cancer Genome Interpreter and OncoKB Database tools were used to find potential actionable targets. Results: We found the most frequent genetic variants, including missense, deletion, duplication, and delins, in the NOTCH4, AR, BARD1, MUC16, and ROS1 genes. Copy Number alterations affected the CDKN2A, CDKN2B, TP53, RHOA, MYC, CCND3, and DDR2 genes mainly in osteosarcoma samples. In four patients, longitudinal analyses of subsequent lesions showed the maintenance of most genomic alterations and enrichment in missense or splice variants in PMS2, SMARCA4, ARID1A, AKT1, BMPR1A, and PTEN, indicating the occurrence of tumor evolution. Germline variants subtraction identified the specific somatic tumor mutations. Advantages and disadvantages of our approach were considered in order to refine the analysis setting and better select possible actionable targets. Conclusions: Early access to genomic analyses, routine germline assessment, and broad gene panels would help in identifying possible targeted drugs with sufficient evidence of activity beneficial to each patient. In the clinical management of advanced sarcoma patients, when analyzing cost-effectiveness and sustainability, the role of the Molecular Tumor Board in the governance of the complexity introduced by mutational oncology should be considered. Full article

Ovarian cancer (OC) remains one of the most lethal gynecologic malignancies due to late diagnosis, rapid progression, and frequent chemoresistance. Despite advances in targeted therapy, durable responses are uncommon, underscoring the need for novel multitarget agents capable of modulating key oncogenic networks. Medicarpin, a natural pterocarpan phytoalexin, exhibits diverse pharmacological activities; however, its molecular mechanisms in OC are poorly defined. This study employed an integrative in silico framework combining network pharmacology, pathway enrichment, molecular docking, and survival analysis to elucidate medicarpin’s therapeutic landscape in OC. A total of 107 overlapping targets were identified, resulting in a dense protein–protein interaction network enriched in kinase-mediated and apoptotic signaling pathways. Ten hub genes were emphasized: CASP3, ESR1, mTOR, PIK3CA, CCND1, GSK3B, CDK4, PARP1, CHEK1, and ABL1. Gene Ontology and KEGG analyses demonstrated substantial enrichment in the PI3K–Akt/mTOR and prolactin signaling pathways. Docking revealed the stable binding of medicarpin to CASP3 (−6.13 kcal/mol) and ESR1 (−7.68 kcal/mol), supporting its dual regulation of hormonal and apoptotic processes. Although CASP3 and ESR1 expression alone lacked prognostic significance, their network interplay suggests synergistic relevance. Medicarpin exhibits multitarget anticancer potential in OC by modulating kinase-driven and hormone-dependent pathways, warranting further experimental validation. Full article

Dermal papilla cells (DPCs) serve as the signaling hub regulating hair follicle (HF) development and cyclical growth. This study aims to investigate the biological function and molecular mechanisms of TGFBR1 (transforming growth factor β receptor 1), a differentially expressed gene identified through single-cell transcriptomic sequencing (scRNA-seq) in the DPCs from fine-wool sheep. Primary DPCs were isolated and purified using a combination of enzymatic digestion and mechanical dissociation, followed by immunofluorescence identification (α-SMA and SOX2-positive). Following successful transfection with constructed TGFBR1 overexpression plasmids and siRNA interference vectors, cell proliferation was assessed via EDU staining and CCK-8 assays. mRNA expression of key genes in Wnt/β-catenin, BMP, and Notch signaling pathways (PCNA, CCND1, CTNNB1, SFRP2, BMP2, NOTCH3, SMAD4, etc.) was validated by RT-qPCR. Single-cell transcriptomics revealed significant downregulation of TGFBR1 in DPCs from fine-wool sheep. Functional validation demonstrated that TGFBR1 overexpression markedly suppressed DPC proliferation, whereas knockdown of TGFBR1 expression promoted DPC proliferation. Molecular mechanism studies showed that TGFBR1 overexpression significantly downregulated PCNA, CCND1, CTNNB1, NOTCH3, and SMAD4 while upregulating SFRP2, BMP2, and TGFB1 expression. These findings demonstrate that TGFBR1 acts as a negative regulator of DPCs proliferation by modulating the activity of multiple signaling pathways, including Wnt/β-catenin, BMP, and Notch, thereby suppressing the proliferative capacity of DPCs. This study not only provides new theoretical support for elucidating the role of the TGF-β signaling pathway in H development but also offers theoretical reference for in-depth research on molecular breeding in ultra -fine-wool sheep and the molecular mechanisms underlying HF development. Full article

Background: The transcription factor FOXM1 is a master regulator of the cell cycle and is implicated in various cell fate decisions. However, its functional role and regulatory network in human Wharton’s jelly mesenchymal stem cells (WJ-MSCs) remain poorly defined. This study aimed to elucidate the comprehensive function of FOXM1 in maintaining WJ-MSC stemness, proliferation, and survival, and to delineate the underlying molecular mechanisms. Methods: We used RNA Interference to knock down FOXM1 in WJ-MSCs. The phenotypic impacts were assessed through CCK-8, colony formation, migration, and flow cytometry assays. We analyzed transcriptomic changes using RNA-seq and verified the results through qRT-PCR and Western blotting. Results: Knockdown of FOXM1 significantly reduced the expression of core pluripotency factors (OCT4, SOX2, and NANOG), impairing stem cell identity and abolishing colony formation and migration capacities. Furthermore, FOXM1 deficiency induced G0/G1 phase cell cycle arrest, downregulated CCND1, and triggered apoptosis through a mechanism involving p53 accumulation, an increased BAX/BCL-2 ratio, and Caspase-3 activation. RNA-seq analysis further corroborated the systematic downregulation of cell cycle pathways and upregulation of apoptotic pathways upon FOXM1 deficiency. Conclusions: Our findings establish FOXM1 as a critical regulatory node that integrates stem cell identity with proliferative and survival signals to maintain WJ-MSC homeostasis. This study redefines FOXM1’s role in stem cell biology and provides a theoretical foundation for enhancing the therapeutic efficacy of WJ-MSCs by modulating this key factor. Full article

Background/objectives: Metaplastic breast carcinoma (MpBC) is a rare, poorly differentiated breast cancer defined by the presence of ductal carcinoma along with areas of matrix-producing, spindle-cell, sarcomatous, or squamous differentiation. It does not express hormone receptors and has a poor overall prognosis. The Hippo molecular pathway was recently related to cancer progression and adjuvant therapy resistance. The objective of this study was to evaluate the expression of Hippo pathway transducers, YAP/TAZ, CCND1, and CTGF, in MpBC and their relation to the clinicopathological characteristics of the disease. Methods: Specimens from patients with MpBC treated at our department from 2003 to 2021 were analyzed utilizing immunohistochemistry and real-time PCR. Results: Forty-four female patients (62.6 ± 14.7 years old) met inclusion criteria and were included in this study. Strong nuclear YAP/TAZ expression was found in 61.4% of patients, while the expressions of CCND1 and CTGF were 3.9% and 12.5%, respectively. Patients presenting at an advanced stage had a statistically worse prognosis compared to the ones diagnosed with stage IA disease. Adjuvant chemotherapy was associated with better overall survival, while disease recurrence was significantly associated with a worse prognosis. Conclusions: Advanced stage at diagnosis and disease recurrence were significantly associated with worse prognosis in MpBC. However, adjuvant chemotherapy significantly led to better overall survival. The Hippo pathway is frequently deregulated (nuclear YAP/TAZ in 61.4% of patients), suggesting it is a compelling novel therapeutic target for this aggressive disease. Full article

Background/Objectives: Oral squamous cell carcinoma (OSCC) often presents at an advanced stage; therefore, the early detection of precursor lesions is crucial. However, the risk assessment of precursor lesions such as oral epithelial dysplasia (OED) remains challenging because of the subjectivity of histopathological grading. We aimed to identify molecular markers that enhance the diagnostic accuracy and prognostic stratification of OSCC and explore the differences in the molecular characterization of OED and OSCC using a few selected markers. Methods: A two-step diagnostic workflow was applied: (1) FISH evaluation of EGFR amplification and CDKN2A deletion to distinguish OED from OSCC and identify EGFR-dependent tumors, and (2) HRAS immunohistochemistry performed exclusively in EGFR-negative OSCCs to stratify EGFR-independent cases. Fluorescence in situ hybridization (FISH) was used to assess seven EGFR/cell cycle-related genes (CCND1, CDKN2A, EGFR, PIK3CA, PTEN, TP53, and 1p36 locus) in 117 formalin-fixed paraffin-embedded samples (66 OED and 51 OSCC) and 10 normal mucosa samples. HRAS expression was evaluated using immunohistochemistry (IHC) in 36 EGFR amplification-negative OSCCs samples. Results:EGFR amplification was frequent in OSCC, whereas CDKN2A deletion was common in OED. The EGFR-amplified/ CDKN2A-intact profile showed high specificity for OSCC and improved diagnostic performance (area under the curve = 0.77) when combined with the Ki-67 labeling index. It also predicted poor disease-free survival (hazard ratio [HR] = 5.08, p = 0.016) and overall survival (HR = 6.10, p = 0.047). Among EGFR-negative OSCCs, HRAS overexpression was associated with advanced-stage disease and a poor prognosis (HR = 6.15, p = 0.043). Conclusions:EGFR amplification was frequent in OSCC, and CDKN2A deletion was prevalent in OED, supporting their use as molecular markers for differential diagnoses. FISH for EGFR/CDKN2A and HRAS IHC can stratify OSCC by diagnosis and prognosis, enabling practical molecular subclassification, including EGFR-negative cases. Full article

Background: Parkinson’s disease (PD) is a complex neurodegenerative disorder in aged people with multifaceted molecular underpinnings. It poses a severe threat to millions of older adults worldwide. The understanding of the molecular mechanisms of PD development and the performance of its therapeutic strategies has not yet reached a satisfactory level. Methods: This study integrated six transcriptomic datasets to uncover key genes (KGs) and their underlying pathogenic mechanisms, providing insights into potential therapeutic strategies for PD. We designed a comprehensive computational pipeline using various bioinformatics tools and databases to investigate PD-causing KGs, focusing on their functions, pathways, regulatory mechanisms, and potential therapeutic drug molecules. Results: In order to explore PD-causing KGs, we initially identified 303 differentially expressed genes (DEGs) between PD and control samples with 204 upregulated and 99 downregulated DEGs using the LIMMA approach with threshold values at Adj. p-value < 0.05 and abs (log₂FC) ≥ 1.0. Then, protein–protein interaction (PPI) network analysis pinpointed seven top-ranked DEGs (GAPDH, PTEN, CCND1, APOE, ESR1, MAPK3/ERK1, and SNCA) as KGs or central modulators of PD pathogenesis. Regulatory network analysis of KGs identified 3 top-ranked transcription factors (FOXC1, NFKB1, and TFAP2A) and 6 microRNAs (hsa-let-7b-5p, hsa-mir-16-5p, and others) as the pivotal regulators of KGs. Gene Ontology (GO) terms and KEGG pathway enrichment analyses with KGs revealed several crucial biological processes, molecular functions, cellular components, and neurodegenerative pathways associated with the development of PD. Finally, the top five molecules guided by KGs (Nilotinib, Bromocriptine, Withaferin-A, Celastrol, and Donepezil) were identified as promising drug candidates against PD and validated computationally through ADME/T analysis and molecular dynamics simulation studies. Conclusions: The findings of this study may serve as valuable resources for developing effective treatment strategies for PD patients. Full article

Background/Objectives: High-grade gliomas (HGGs), including glioblastomas, are among the most aggressive brain tumors due to their high intratumoral heterogeneity and extensive infiltration. Glioma stem-like cells (GSCs) frequently invade along white matter tracts such as the corpus callosum, but the molecular programs driving this region-specific invasion remain poorly defined. The aim of this study was to identify transcriptional signatures associated with GSC infiltration into the corpus callosum. Methods: We established an orthotopic xenograft model by implanting fluorescently labeled human GSCs into nude mouse brains. Tumor growth and invasion patterns were assessed using tissue clearing, light-sheet fluorescence microscopy, and histological analyses. To characterize region-specific molecular profiles, we performed microfluidic-based single-cell RNA expression analysis of 48 invasion- and stemness-related genes in cells isolated from the tumor bulk (TB) and corpus callosum (CC). Results: By six weeks post-implantation, GSCs displayed marked tropism for the corpus callosum, with distinct infiltration patterns captured by three-dimensional imaging. Single-cell gene expression profiling revealed significant differences in 7 of the 48 genes (14.6%) between TB- and CC-derived GSCs. These genes—NES, CCND1, GUSB, NOTCH1, E2F1, EGFR, and TGFB1—collectively defined a “corpus callosum invasion signature” (CC-Iv). CC-derived cells showed a unimodal, high-expression profile of CC-Iv genes, whereas TB cells exhibited bimodal distributions, suggesting heterogeneous transcriptional states. Importantly, higher CC-Iv expression correlated with worse survival in patients with low-grade gliomas. Conclusions: This multimodal approach identified a corpus callosum-specific invasion signature in glioma stem-like cells, revealing how local microenvironmental cues shape transcriptional reprogramming during infiltration. These findings provide new insights into the spatial heterogeneity of gliomas and highlight potential molecular targets for therapies designed to limit tumor spread through white matter tracts. Full article

Background: Cholangiocarcinoma (CCA) is an aggressive cancer of biliary tract with poor prognosis and limited therapeutic alternatives. While targeted medicines only benefit a small subset of patients with specific genetic modifications, conventional chemotherapy offers negligible survival advantages. There is an urgent need for novel medicines with multi-target action to combat the diverse and treatment-resistant characteristics of CCA. Methods: An integrative computational strategy combining drug-likeness evaluation, target prediction, network pharmacology, Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) enrichment analyses, and molecular docking was employed to elucidate the pharmacological profile of medicarpin, a natural pterocarpan derived from Dalbergia species. Overlapping targets between medicarpin and CCA-related genes were analysed to construct a protein–protein interaction (PPI) network and identify hub genes. Results: Forty-four overlapping targets were identified, with mTOR, SRC, PIK3CA, and CCND1 emerging as central nodes within the network. Enrichment analyses revealed significant involvement in carcinogenic pathways, including PI3K–Akt/mTOR, ErbB signalling, apoptosis regulation, and drug resistance. Molecular docking demonstrated a stable binding of medicarpin within the catalytic pocket of mTOR (binding energy −9.6 kcal/mol), supported by multiple hydrogen bonds and hydrophobic interactions with key residues essential for kinase activation. Conclusions: This study provides systems-level evidence that medicarpin exerts polypharmacological activity against CCA, with mTOR indicated as a possible mechanistic hub. These findings highlight medicarpin’s potential as a promising multi-target therapeutic candidate and underscore the value of natural compounds in expanding treatment strategies for cholangiocarcinoma. Full article

The formation of the Chinese three-keeled pond turtle (Mauremys reevesii) carapace is a complex biological event involving developmental processes such as collagen deposition and ossification. As a key regulator of collagen deposition and ossification, Col10a1 may play a crucial role in carapace development, though its specific mechanism remains unclear. To investigate the role of Col10a1 during carapace development and its regulatory mechanisms, we cloned its cDNA sequence and performed bioinformatic analysis. This revealed that Col10a1 encodes a stable, hydrophilic, and basic protein, with phylogenetic analysis showing closest evolutionary relationships to other reptiles and the greatest divergence from fish. Further RT-qPCR analysis examined Col10a1 expression patterns in M. reevesii embryos at stages 14, 18, and 22, as well as in various tissues of adult males and females. Results indicated that during embryonic development, Col10a1 expression levels progressively increased alongside the progression of carapace ossification and collagen deposition, suggesting its involvement in regulating this process. In adult tissues, Col10a1 exhibited widespread expression, with particularly high levels in the brain, kidneys, and liver, suggesting potential specialized functions in these organs. Finally, in vitro experiments demonstrated that inhibition of the Wnt/β-catenin pathway with salinomycin sodium salt downregulated the expression of both its target genes (Sp5, Myc, Ccnd1) and Col10a1. In contrast, inhibition of the TGF-β/Smad pathway with oxymatrine suppressed its target genes (Serpine1, Cdkn1a) but concomitantly upregulated Col10a1. These results suggest that Col10a1 expression may be positively regulated by the Wnt/β-catenin pathway and negatively regulated by the TGF-β/Smad pathway. Our findings provide novel insights into the molecular mechanisms governing carapace development and collagen deposition in M. reevesii, laying a crucial foundation for further investigations into the regulatory networks involving Col10a1 during carapace formation. Full article

Current therapeutic strategies for IgE-mediated diseases are limited. The drawbacks include adverse reactions, ineffectiveness, and relapses. Natural compound berberine (BBR) may combat this therapeutic gap through sustained transcriptional regulation of IgE. Human tonsil cells were cultured in the presence or absence of BBR to establish dose-dependent effects on IgE, IgG, and cell viability. IgE-producing plasma cells (U266, IgE plasma cells) and IgG-producing plasma cells (ARH-77, IgG plasma cells) were used as surrogate cells to validate dose-dependent effects on IgE and IgG production, respectively. At 10 μg/mL BBR, cell viability and proliferation were determined, and cells were harvested for protein, RNA, and miRNA and analyzed by Western blot and qPCR. BBR treatment of human tonsil samples resulted in reduced IgE production (p < 0.001) with no effect on IgG levels or cell viability. BBR demonstrated sustained, dose-dependent inhibition of IgE production by IgE plasma cells (p < 0.001), without affecting IgG production by IgG plasma cells. There was no significant reduction in cell viability of either cell type. Proliferation was reduced in IgE plasma cells (p = 0.02), but not IgG plasma cells. Assessment of IgE regulation and cell cycle at the RNA level revealed that BBR reduced IgE heavy chain expression and CCND1 (p < 0.01), with increased the GADD45A expression of IgE plasma cells, only (p = 0.016). At the protein level, BBR increased p53 (p = 0.02) and CDKN1C (p = 0.03), and decreased CDK2 (p = 0.01) expression of IgE plasma cells, only. Investigation of miRNAs implicated in B cell and p53 regulation demonstrated increased p53 and GADD45A activator, miR-34a (p = 0.04). miRNAs that are present in IgE plasma cells allow for specific effects on B cells and cell cycle genes by BBR, that are not present in IgG plasma cells. A novel mechanism for specific suppression of IgE by BBR highlights miR-34a, involved in the p53 pathway and B cell development, and may be crucial to pathological IgE production. Full article

Background: Non-small cell lung cancer (NSCLC) progression is driven by dysregulated competing endogenous RNA (ceRNA) networks, where non-coding RNAs sequester miRNAs to modulate oncogene expression. The tumor-suppressor miR-145 is frequently downregulated in NSCLC, but its lncRNA-mediated regulation remains incompletely characterized. Methods: Integrated transcriptomic analysis of NSCLC datasets (GSE135304: blood RNA from 712 patients; GSE203510: plasma miRNAs) was used to identify dysregulated genes (|log2FC| > 0.1, p < 0.05) and miRNAs (|log2FC| > 1, p < 0.05). Experimentally validated targets from miRTarBase/TarBase were intersected with dysregulated genes, followed by WikiPathways/GO enrichment. ceRNA networks were constructed via co-expression analysis. RT-qPCR validated miR-145-3p expression in A549/MRC-5 cells and NSCLC tissues. GEPIA assessed FN1/CCND1 clinical relevance. Results: We identified 8271 dysregulated genes and 52 miRNAs. miR-145-3p, critical in immune regulation, was significantly downregulated (log2FC = −1.24, p = 0.036). Intersection analysis revealed 27 miR-145-3p targets (e.g., FN1, CCND1, SMAD3) enriched in immune pathways (FDR < 0.05) and TGF-β-mediated EMT within the dysregulated geneset. Six immune-linked hub genes emerged. LncRNAs LOC729919 and LOC100134412 showed strong co-expression with hub genes and competitively bind miR-145-3p, derepressing the expression of the metastasis drivers FN1 (ECM regulator) and CCND1 (cell cycle controller). This ceRNA axis operates within a broader dysregulation of ATM-dependent DNA damage, Hippo signaling, and cell cycle pathways. RT-qPCR confirmed significant miR-145-3p suppression in NSCLC models (p < 0.05). GEPIA revealed a significant FN1-CCND1 co-expression (p = 0.0017). Conclusions: We characterize a novel LOC729919/LOC100134412–miR-145–FN1/CCND1 ceRNA axis in NSCLC pathogenesis. FN1’s prognostic value and functional linkage to CCND1 underscores its potential clinical relevance for therapeutic disruption. Full article

This study investigates the regulatory role of circFBN1 in chicken follicular granulosa cells (GCs) and its underlying molecular mechanisms through the miR-206/E2F5 pathway. circFBN1 was found to significantly enhance GC proliferation and inhibit apoptosis, as evidenced by increased expression of proliferation-related genes (PCNA, CDK1, and CCND1) and decreased expression of apoptosis-related genes (Caspase-3). Additionally, circFBN1 overexpression promoted the secretion of estradiol (E2) and progesterone (P4) by upregulating steroidogenesis-related genes (StAR and CYP11A1). Mechanistic studies revealed that circFBN1 functions as a molecular sponge for miR-206, thereby alleviating its inhibitory effect on the target gene E2F5. Dual-luciferase reporter assays confirmed the specific binding between circFBN1 and miR-206. Overexpression of miR-206 had the opposite effects, inhibiting GC proliferation, inducing apoptosis, and reducing E2 and P4 secretion by downregulating StAR and CYP11A1. Furthermore, E2F5 was identified as a direct target of miR-206, and its knockdown significantly reduced GC proliferation, increased apoptosis, and decreased steroid hormone secretion. These findings elucidate the regulatory mechanisms of the circFBN1/miR-206/E2F5 axis in avian follicle development and provide potential molecular targets for improving poultry reproductive performance. Future research should focus on exploring the upstream regulators of this axis and its interactions with other signaling pathways. Full article