Search Results (11,744)

Background: Pituranthos scoparius (Apiaceae), commonly known in Algeria as “Kozah”, is a medicinal plant traditionally used for various therapeutic purposes. However, its potential as a source of antiproliferative agents and its underlying molecular mechanisms remain poorly characterized. Purpose: This study aimed to investigate the antiproliferative potential of P. scoparius through an integrated strategy combining phytochemical profiling, in vitro evaluation, and computational approaches, with particular emphasis on its activity against key cancer-related pathways. Study Design: An integrated experimental–computational study was performed to explore the multitarget antiproliferative profile of P. scoparius extracts. Methods: Phytochemical characterization was carried out using LC-MS/MS and GC-MS/MS to identify the major bioactive constituents. Antiproliferative activity was assessed in vitro against human colorectal (HT-29) and hepatocellular carcinoma (HepG2) cell lines using the MTT assay. Molecular docking studies were conducted on selected major metabolites against relevant oncogenic targets, including PI3Kα, mTOR, COX-2, and BCL-2, to investigate potential mechanisms of action. Machine learning approaches were further employed to support the prediction of multitarget antiproliferative activity. Results: Chlorogenic acid and trans-ferulic acid were identified as the predominant phenolic compounds, while α-pinene was the major constituent of the essential oil. Both preparations exhibited significant dose- and time-dependent antiproliferative effects, with the essential oil showing enhanced cytotoxicity (IC₅₀ up to 35.4 µg/mL). In silico analyses revealed strong binding affinities of key metabolites toward critical oncogenic proteins, particularly within the PI3Kα/mTOR signaling pathway. Machine learning predictions further supported a multitarget antiproliferative profile. Conclusions: P. scoparius represents a promising source of natural compounds with multitarget antiproliferative potential. The combined experimental and computational findings provide mechanistic insights into its activity and support its relevance within the context of natural product-based cancer therapy, highlighting its potential for further preclinical development. Full article

Background/Objectives: Fusion-positive rhabdomyosarcoma (FP-RMS) is characterized by the presence of tumor-specific chromosomal translocation products, most commonly PAX3::FOXO1, and typically results in lower survival rates compared to fusion-negative RMS cases. PAX3::FOXO1 plays a critical role in FP-RMS oncogenesis in both tumor initiation and maintenance, making it an excellent target for therapeutic intervention in FP-RMS. Methods: We created Proteolysis Targeting Chimeras (PROTACs) by combining PAX3::FOXO1-binding small molecules with E3 ligase recruiters for cereblon (CRBN) or S-Phase Kinase Associated Protein 1 (SKP1). Results: The PROTACs achieved up to 70% degradation of the endogenous PAX3::FOXO1 protein in FP-RMS cell lines in a concentration-, time-, and proteasome-dependent manner. Moreover, the PROTAC-mediated targeted degradation of PAX3::FOXO1 in FP-RMS cells deregulated the endogenous PAX3::FOXO1 gene expression signature and induced myogenic differentiation. Importantly, treatment of FP-RMS cells with PAX3::FOXO1-PROTACs synergized with vincristine treatment and impaired >80% of anchorage-independent growth in soft agar. Conclusions: Taken together, we demonstrate the proof of principle of PROTACs targeting the oncogenic fusion protein PAX3::FOXO1 in FP-RMS cells. The PROTACs created in this study will not only be useful tools in studying PAX3::FOXO1 biology in laboratory models but could also serve as molecular scaffolds for designing clinical-grade molecules to assess the therapeutic potential of PAX3::FOXO1-targeting PROTACs in FP-RMS patients. Full article

Lead (Pb) pollution is a global public health issue, yet the mechanisms underlying Pb-induced kidney aging remain poorly understood. Selenium (Se), an essential trace element critical for kidney health, primarily exerts its physiological roles via selenoproteins; among them, membrane-bound selenoproteins strategically localized at the endoplasmic reticulum and plasma membrane, have emerged as potential molecular links in Se-mediated protection. In this study, Hyline chicken models (treated with 350.00 mg/L Pb or/and 1.00 mg/kg Se) and HK-2 cell models (treated with 200 μM Pb or/and 2.5 μM Se) were established to investigate the protective mechanism of Se to Pb poisoning in kidneys, with emphasis on membrane-bound selenoproteins and kidney aging. Results showed that Pb significantly decreased (p < 0.05) membrane-bound selenoproteins and induced kidney aging. Inflammation and autophagy were involved, as Pb significantly increased (p < 0.05) pro-inflammatory cytokines interleukin-4 (IL-4) and interleukin-12β (IL-12β), and autophagy-related genes autophagy related 5 (ATG5), BCL2 interacting coiled coil protein 1 (Beclin 1), and microtubule-associated protein 1A/1B-light chain 3 (LC3-II) while significantly suppressing (p < 0.05) interleukin-2 (IL-2) and mammalian target of rapamycin (mTOR). Se had a relieving effect on it, as evidenced by significantly reversing (p < 0.05) the changes in the above indicators. Interestingly, Selenoprotein T (SELENOT), as a hub membrane-bound selenoprotein, is sensitive to Pb poisoning (Pb exposure decreased SELENOT mRNA expression to 56%, 34%, and 19% of the control levels at 30, 60, and 90 days, respectively). Knockdown of SELENOT aggravated Pb-induced inflammation, autophagy, and cellular senescence, meaning that SELENOT protected against kidney aging via suppressing inflammation and autophagy under Pb stress. These findings establish membrane-bound selenoproteins as essential molecular hubs that orchestrate inflammation resolution and autophagy in Se’s antagonism against Pb-induced kidney aging, highlighting promising therapeutic targets for nephropathy. Full article

A bidirectional relationship has been observed between COVID-19 and respiratory disorders, where respiratory comorbidities increase severity, and COVID-19 induces respiratory sequelae. The underlying biological and genetic mechanisms remain unclear. While previous studies have identified overlapping genetic loci, few have systematically disentangled the genetic factors shared between these conditions versus those specific to COVID-19, particularly at a multi-omics level. We developed and applied a unified analytical framework to compare three COVID-19 phenotypes with eight respiratory disorders (including asthma, COPD, IPF, and pneumonia). Utilizing the cofdr method for shared genetic signal analysis and DDx/mtCOJO for differentiation, we integrated genome-wide association statistics with multi-omics data (transcriptome, splicing, and proteome). This approach allowed for the simultaneous identification of shared genetic signals (concordant or discordant) and disease-specific variants across expression (TWAS), alternative splicing (spTWAS), and protein abundance (PWAS). We delineated a comprehensive atlas of 214 differential and numerous shared loci across 24 pairwise comparisons. The shared genetic architecture was characterized by pleiotropic effects in genes such as ATP11A (exhibiting opposing effects in COVID-19 vs. IPF) and GSDMB (shared with COPD). Crucially, differentiation analysis revealed that severe COVID-19 is genetically distinct from other respiratory infections (e.g., pneumonia and influenza) through dysregulated Type I/III interferon signaling and specific defects in alveolar epithelial and macrophage function, as well as GM-CSF/surfactant metabolism pathways. These findings provide human genetic evidence consistent with the therapeutic rationale underlying GM-CSF modulators and interferon-lambda for COVID-19, both of which have entered clinical trials. Furthermore, multi-trait conditional analysis prioritized FYCO1 and HCN3 as potential COVID-19-specific risk genes. Splicing analysis underscored the critical role of alternative splicing in both shared and differential architectures, highlighting IFNAR2 isoform regulation as a key discriminator between COVID-19 and other respiratory traits. This study provides the first genome-wide, multi-omics map revealing the shared and differential genetic landscapes of COVID-19 and other respiratory phenotypes. By uncovering specific molecular mechanisms that distinguish COVID-19 pathology, specifically involving surfactant homeostasis and interferon pathways, our findings offer novel insights for targeted drug repurposing and precision risk stratification. Full article

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is an idiopathic, multisystem disorder marked by debilitating fatigue, post-exertional malaise, cognitive dysfunction and neuroinflammation. Its etiology remains unclear, yet emerging evidence implicates a complex interplay between immune dysregulation, metabolic impairment, mitochondrial bioenergetics, and environmental stressors such as viral infection or low-dose ionizing radiation (LDIR). To develop treatments for ME/CFS, it is essential to identify suitable targets for therapy. In this narrative review, we discuss recent findings on the overlap of ME/CFS with LDIR effects and examine potential mechanistic links that may arise from LDIR-induced bystander effects (RIBEs). We highlight potential candidate biomarkers that bridge these domains: mitochondrial respiratory dysfunction, altered ornithine transport via SLC25A15 (ORNT1), possible roles of CD38 in the context of immunity and NAD+ depletion, cyclin D1–dependent metabolic reprogramming and modulation of gene expression, and α-synuclein as a potential neuroinflammatory damage-associated molecular pattern (DAMP). While the involvement of these biomarkers in ME/CFS is yet to be confirmed experimentally, evidence from in vitro studies of irradiated cells, exosome profiling, and patient samples suggests that RIBEs can, in theory, produce prominent cellular ME/CFS phenotypes through associated mechanisms, including those exhibiting oxidative stress, impaired ATP production, and immune modulation. We propose a hypothetical, exploratory model wherein LDIR initiates or contributes to adaptive metabolic shifts (including CD38 upregulation and cyclin D1 stabilization) that, coupled with persistent bystander signaling, could potentially culminate in chronic fatigue and neurocognitive symptoms in some reported ME/CFS cases. Finally, we outline a research agenda encompassing the establishment of standardized diagnostic criteria, multi-omics profiling of patient cohorts, exosome analysis, functional mitochondrial assays, and targeted therapeutic trials focusing on possible anti-CD38 antibodies and NAD+ precursor therapy. By integrating recent findings in low-dose radiation biology with ME/CFS pathophysiology, this review aims to promote interdisciplinary investigations that may uncover mechanistic insights and novel biomarkers for diagnosis and treatment of ME/CFS. We further review steps in a proposed model taking us from low-dose radiation exposure to a number of possible targets. Full article

Cancer progression is driven by dysregulated kinase signaling and apoptotic evasion across multiple malignancies. Although targeted kinase inhibitors have improved outcomes, resistance and toxicity remain major challenges. Natural phytochemicals offer promising multi-target therapeutic potential. Persea americana contains diverse bioactive compounds; however, its role in multi-cancer kinase targeting remains underexplored. This study aimed to identify and validate anti-cancer kinase targets of Persea americana phytoconstituents across five cancers: lung, breast, cervical, colorectal, and prostate, using integrated network pharmacology and molecular simulation approaches. Cancer-associated genes were retrieved from the Open Targets Platform and prioritized through Gene Ontology analysis. Overlapping targets with 208 predicted human targets of Persea americana were identified. Protein–protein interaction networks revealed hub genes, followed by TCGA-based validation. Twenty-five phytoconstituents were docked against SRC and GSK3β, and top complexes underwent 100 ns molecular dynamics simulations. Enrichment highlighted kinase activity and apoptosis. SRC emerged as a pan-cancer hub, while GSK3β was prominent in breast cancer. Luteolin showed strongest binding to SRC (−11.9 kcal/mol), outperforming the co-crystal inhibitor, while valencene showed affinity toward GSK3β (−8.8 kcal/mol). Simulations confirmed stable interactions. Luteolin exhibits strong multi-target kinase inhibition, particularly against SRC, supporting its potential as a pan-cancer therapeutic candidate. Full article

Breast cancer remains one of the most prevalent malignancies affecting women worldwide and continues to be a leading cause of cancer-related morbidity and mortality. Patients may present with either localized or advanced disease, with clinical outcomes increasingly influenced by molecular subtype and genetic profile. This review highlights the key genetic factors involved in breast cancer, current diagnostic and therapeutic strategies, and promising emerging approaches that may shape future clinical management. Breast cancer diagnosis typically involves clinical breast examination, imaging techniques such as mammography and ultrasound, and confirmatory biopsies. Genetic mutations in specific genes are strongly linked to the development, progression, and metastasis of the disease. Treatment options for localized breast cancer continue to include surgery (lumpectomy or mastectomy) and radiotherapy, combined with systemic therapies tailored to tumor biology, such as endocrine therapy, human epidermal growth factor receptor 2 (HER2)-targeted therapy, and cyclin-dependent kinase (CDK)4/6 inhibitors. For advanced or metastatic breast cancer, recent therapeutic advances include the use of immunotherapy (e.g., immune checkpoint inhibitors), Poly (ADP-ribose) polymerase (PARP) inhibitors for Breast Cancer gene (BRCA)-mutated cancers, antibody–drug conjugates, and novel targeted agents, which have significantly improved patient outcomes in selected populations. Recent findings in breast cancer genetics have highlighted the critical role of germline and somatic mutations, particularly in genes such as BRCA1, BRCA2, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), and TP53, in driving tumor initiation, progression, and therapeutic response. Molecular profiling and next-generation sequencing technologies have enabled more precise tumor classification and facilitated the development of personalized treatment strategies. Despite these advances, treatment resistance and disease recurrence remain major challenges, particularly in aggressive subtypes such as triple-negative breast cancer. Consequently, ongoing research is exploring alternative and complementary approaches, including nanotechnology-based drug delivery systems, gene editing techniques such as clustered regularly interspaced short palindromic repeats-Cas9 (CRISPR-associated protein 9) (CRISPR-Cas9), cancer vaccines, and the integration of traditional and plant-derived compounds. These strategies aim to enhance therapeutic efficacy, reduce systemic toxicity, and overcome resistance mechanisms. Full article

Chalcones are naturally occurring open-chain flavonoids widely distributed in plants and recognized for their broad spectrum of pharmacological activities. Their versatile scaffold allows for extensive structural modifications, leading to a diverse range of natural and synthetic derivatives with notable biological potential. In the context of viral infections, chalcones have demonstrated remarkable efficacy against a variety of human pathogens, including dengue virus, HIV, HCV, influenza A, SARS-CoV-2, and other emerging viruses. Beyond human health, several chalcones have shown potent activity against plant viruses such as tobacco mosaic virus (TMV) and cucumber mosaic virus (CMV), and animal viruses including porcine reproductive and respiratory syndrome virus (PRRSV) and mammalian reovirus (MRV), underscoring their broad antiviral spectrum. These compounds act through multiple mechanisms, including the inhibition of viral enzymes (e.g., proteases, polymerases, and integrases), interference with viral entry and replication, and the modulation of host-related pathways. Recent advances in molecular docking, structure–activity relationship (SAR) studies, and synthetic optimization have further highlighted chalcones as a promising scaffold for antiviral drug discovery. Accordingly, this review summarizes and categorizes antiviral chalcones reported over the last two decades, emphasizing and critically discussing their molecular targets, mechanisms of action, and pharmacological potential as lead compounds. It also provides a comparative perspective on their pharmacological relevance by correlating their activities against standard therapeutic agents and reference inhibitors. Furthermore, the most recurrent viral targets were critically discussed regarding their conservation, expected genetic barriers to resistance, and the global SAR trends identified for the corresponding antiviral chalcones. Finally, in silico ADMET profiling of the most promising naturally occurring chalcones was performed to evaluate their drug-likeness and pharmacokinetic properties, offering guidance for future structural optimization and translational development. Collectively, these findings highlight the chalcone scaffold as a versatile platform for the development of novel antiviral agents targeting diverse viral and host pathways. Full article

Prostate cancer remains a major cause of cancer-related mortality, and new therapeutic strategies are needed for advanced disease. Niclosamide and related salicylanilide compounds have emerged as multitarget anticancer agents, but the molecular contexts associated with their activity remain incompletely understood. Here, we applied a phenotype-oriented integrative framework to characterize the molecular context and phenotypic activity of NSC828786, a niclosamide-like salicylanilide derivative. Cross-cohort transcriptomic analyses identified AMACR (alpha-methylacyl-CoA racemase) and HPN (hepsin) as consistently upregulated genes in independent prostate adenocarcinoma cohorts. NCI-60 profiling demonstrated broad-spectrum low-micromolar antiproliferative activity, including AR-negative prostate cancer and breast cancer cell lines spanning multiple receptor subtypes; however, quantitative ranking did not support preferential receptor subtype selectivity. CellMiner COMPARE analysis showed no significant correlation between baseline AMACR or HPN expression and NSC828786 sensitivity. Structure-based analyses supported computational compatibility of NSC828786 with predicted HPN- and AMACR-associated binding regions, while zebrafish assays showed no overt developmental abnormalities at concentrations ≤ 5 μM. These findings identify NSC828786 as a phenotypically active salicylanilide derivative and position HPN and AMACR as exploratory candidate molecular associations warranting further mechanistic and target engagement studies. Full article

Background: Geraniol is an acyclic monoterpene widely distributed in the essential oils of aromatic species such as Cymbopogon citratus, Pelargonium graveolens, and Rosa damascena, It is known for its antioxidant, anti-inflammatory, neuroprotective, and antitumor activities. Methods: This study aimed to investigate, through network pharmacology and computational ADMET modeling, the molecular mechanisms and pharmacological potential of geraniol, integrating drug-likeness parameters, toxicity prediction, and multitarget interactions. Results: A total of 25 core targets were identified, mainly involved in inflammation, oxidative stress, apoptosis, and transcriptional regulation. Geraniol exhibited a favorable drug-likeness profile, high predicted intestinal absorption, and low systemic toxicity, supporting its pharmaceutical applicability. Mechanistically, it modulates the Nrf2/HO-1 ↔ NF-κB axis, reducing reactive oxygen species, pro-inflammatory cytokines (TNF-α, IL-1β, IL-6), and apoptotic markers (caspases, Bax), while enhancing antioxidant enzymes (SOD, CAT, GPx) and antiapoptotic proteins (Bcl-2). Conclusions: These findings confirm its multitarget and pleiotropic nature, highlighting its potential as a therapeutic candidate for inflammatory, metabolic, and neurodegenerative disorders. Furthermore, this study provides a robust mechanistic rationale for future in vitro and in vivo validation, as well as for the design of nanostructured formulations to improve geraniol’s bioavailability and therapeutic safety. Full article

Background: Despite therapeutic advances, many patients with metastatic lung cancer still lack access to comprehensive molecular profiling, often due to inadequate biopsy samples. Percutaneous ultrasound-guided needle aspiration biopsy (US-NAB) from both lung and metastatic sites has shown promise in improving diagnostic and molecular profiling accuracy. However, data regarding its real-world utilization, diagnostic performance, and contribution to comprehensive molecular profiling in unselected patients with advanced lung cancer remain limited. Methods: We performed a secondary (post hoc) analysis of prospectively collected data from the Propheta Pro study, a prospective observational cohort of patients with advanced lung cancer. The aim of the present analysis was to assess patterns of invasive sampling procedures, with a particular focus on the prevalence of US-NAB utilization across histologic subtypes. We also assessed the diagnostic yield of US-NAB for cancer diagnosis, comprehensive genomic profiling, and PD-L1 expression. Results: Among the 348 patients enrolled, 123 (35.3%) underwent US-NAB, making it the most frequently utilized sampling technique overall and across individual histologic subtypes. Biopsy of metastatic sites was significantly more common than primary lung tumors (113, 91.9% versus 10, 8.1%; p < 0.001), with superficial metastases being the primary target (110, 89.4%). US-NAB demonstrated high diagnostic yields: 97% for histological diagnosis, 91.1% for comprehensive genomic profiling, and 95.8% for PD-L1 testing. Only two minor, self-limiting complications were observed. Conclusions: US-NAB is a highly effective yet underrecognized diagnostic option for advanced lung cancer, particularly given the high prevalence of accessible superficial metastases. Integrating US-NAB into interventional pulmonology services could enhance diagnostic and molecular profiling yields. Full article

Background/Objectives: Chronic myeloid leukemia (CML) is a hematological malignancy driven by the constitutively active BCR-ABL1 fusion protein. Although current ABL1 tyrosine kinase inhibitors (TKIs) have improved CML management, resistance remains a major challenge, highlighting the need for novel therapeutic strategies. Methods: A chalcone derivative containing naphthalene and toluene moieties (A) was synthesized from 2-acetonaphthone and p-tolualdehyde and subsequently converted into a novel 4,5-dihydro-1H-pyrazole-1-carbothioamide derivative (B) through reaction with thiosemicarbazide. The cytotoxicity of compounds A and B against K562 CML cells was evaluated using the MTT assay. The active compound was further investigated for cytotoxic selectivity using HL-60 acute myeloid leukemia (AML) cells and healthy PBMCs. Apoptotic effects in K562 cells were analyzed using Annexin V/ethidium homodimer staining, whereas ABL1 inhibitory activity was determined using the ADP-Glo kinase assay. The potential interaction between the active compound and ABL1 was assessed by molecular docking analysis. Results: Compound B displayed potent cytotoxic activity against K562 cells with an IC₅₀ value of 6.92 ± 1.14 µM and demonstrated selectivity toward leukemic cells over PBMCs (SI = 5.4). Treatment with compound B markedly induced apoptosis in K562 cells. In addition, compound B inhibited ABL1 activity in a concentration-dependent manner. Molecular docking studies revealed a favorable binding orientation within the ATP-binding pocket of ABL1. Furthermore, in silico absorption, distribution, metabolism, and excretion (ADME) analysis predicted favorable pharmacokinetic properties for compound B. Conclusions: These findings demonstrate that compound B possesses cytotoxic, pro-apoptotic, and ABL1 inhibitory activities against CML cells and may serve as a promising lead structure for the development of novel therapeutic agents targeting CML. Full article

Most cancers are fatal and remain challenging to cure due to changes in tumorigenesis and therapeutic resistance. Despite significant advancements in cancer therapy, a substantial proportion of malignancies exhibit resistance to conventional therapies, driven primarily by cancer plasticity and the emergence of multidrug resistance. Recent cancer treatments include cytotoxic chemotherapy, molecular targeted therapy, and immune checkpoint inhibitors. A major hallmark of cancer cells is their ability to develop sophisticated evasion mechanisms that bypass programmed cell death when exposed to anti-cancer drugs. In addition, malignant cells evade the efficacy of anti-cancer drugs by altering cell proliferation, survival, and metastasis. To suppress oncogenic characteristics, necroptosis-based therapies have attracted substantial attention, as they can inhibit tumorigenesis and improve treatment outcomes across many cancer types. Furthermore, an increasing body of research focuses on suppressing tumorigenesis by targeting receptors that are overexpressed in cancer cells. In this review, we elucidate how tumorigenesis is inhibited by regulating the epidermal growth factor receptor (EGFR)–tumor necrosis factor receptor (TNFR) signaling pathway in necroptosis. By delineating the underlying mechanisms of these receptors, we propose that the induction of necroptosis via EGFR and TNFR represents an innovative paradigm for targeted therapy, offering a strategy to enhance clinical outcomes in treatment-resistant cancers. Full article

Inflammation-induced placental dysfunction is a major contributor to pregnancy complications. Activation of NF-κB and NLRP3 inflammasome pathways in the placenta is a key driver of this pathology. Decursinol, a natural coumarin derivative from Angelica gigas, possesses anti-inflammatory properties; however, its effect on placental inflammation remains unclear. Therefore, in this study, we investigated the protective effects of decursinol against lipopolysaccharide (LPS)-induced placental inflammation and trophoblast dysfunction and explored the underlying molecular mechanisms. Decursinol significantly inhibited LPS-induced NLRP3 inflammasome activation and NF-κB/p65 signaling in Sw.71 human trophoblast cells, reducing interleukin-1β secretion and pro-inflammatory gene expression. It restored the trophoblast invasive capacity and preserved mesenchymal marker expression suppressed by LPS. It also improved the fetal and placental weights, restored the placental architecture, and attenuated placental NLRP3 inflammasome activation and cytokine expression in vivo. Mechanistically, decursinol preserved the mitochondrial homeostasis, reduced mitochondrial reactive oxygen species levels, and upregulated antioxidants and mitochondrial biogenesis-related gene levels, exerting effects comparable to those of mitochondria-targeted antioxidant Mito-TEMPO. These findings suggest that decursinol protects against LPS-induced trophoblast dysfunction and adverse pregnancy outcomes by preserving mitochondrial functions and suppressing NLRP3/NF-κB-mediated inflammation. Overall, our results highlight decursinol as a promising therapeutic candidate for inflammation-associated pregnancy complications. Full article

Background/Objectives: Rhabdomyosarcoma (RMS), the most common pediatric soft tissue sarcoma, includes two main subtypes, embryonal (eRMS) and alveolar (aRMS), each with distinct molecular and clinical characteristics. Although cellular processes underlying RMS and differences between PAX3-FOXO1 fusion-positive and fusion-negative tumors are well known, the contribution of long noncoding RNAs (lncRNAs) remains poorly understood. Methods: Here, we reannotated publicly available microarray datasets to comprehensively profile lncRNA expression and reconstruct lncRNA–miRNA–mRNA regulatory networks in RMS. Results: We identified several lncRNAs with subtype-specific differential expression, including HOTAIR as a potential sponge for miR-206, DSCR8 for miR-885-5p, and PRKCQ-AS1 for miR-515-5p in eRMS. Database-supported interaction analyses identified putative regulatory relationships between these lncRNAs and cancer-related miRNAs and mRNAs. Validation using the St. Jude Cloud PeCan platform confirmed distinct lncRNA expression signatures across RMS subtypes and other pediatric solid tumors, supporting subtype-specific regulation. Conclusions: Our findings provide an updated characterization of the lncRNA landscape in RMS and identify candidate lncRNA–miRNA–mRNA regulatory networks that may contribute to disease biology. The proposed regulatory interactions are hypothesis-generating and require experimental validation. Overall, our findings provide a resource for future functional studies and support the investigation of lncRNAs as potential biomarkers and therapeutic targets in RMS. Full article