Search Results (160)

Lead (Pb) exposure poses a significant public health concern due to its neurotoxic effects. While mitochondrial dysfunction is implicated in lead neurotoxicity, the precise molecular mechanisms, particularly the role of non-coding RNA-mediated competing endogenous RNA networks, remain underexplored. SH-SY5Y neuroblastoma cells were treated with 10 μM lead acetate. Cell viability was assessed by Cell Counting Kit-8 (CCK-8). Mitochondrial ultrastructure and quantity were analyzed via transmission electron microscopy (TEM). Key mitochondrial dynamics proteins were examined by Western blot. Comprehensive transcriptome sequencing, including long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), microRNAs (miRNAs) and mRNAs, was performed followed by functional enrichment and ceRNA network construction. Selected RNAs and hub genes were validated using quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). Lead exposure significantly reduced SH-SY5Y cell viability and induced mitochondrial damage (decreased quantity, swelling, fragmentation). Western blot confirmed an imbalance in mitochondrial dynamics, as indicated by decreased mitofusin 2 (MFN2), increased total and phosphorylated dynamin-related protein 1 (DRP1). Transcriptomic analysis revealed widespread differential expression of lncRNAs, circRNAs, miRNAs, and mRNAs. Enrichment analysis highlighted mitochondrial function and oxidative stress pathways. A ceRNA network identified five key hub genes: SLC7A11, FOS, HMOX1, HGF, and NR4A1. All validated RNA and hub gene expression patterns were consistent with sequencing results. Our study demonstrates that lead exposure significantly impairs mitochondrial quantity and morphology in SH-SY5Y cells, likely via disrupted mitochondrial dynamics. We reveal the potential regulatory mechanisms of lead-induced neurotoxicity involving ceRNA networks, identifying hub genes crucial for cellular stress response. This research provides a foundational framework for developing therapeutic strategies against lead-induced neurotoxicity. Full article

Kazakh mares have drawn significant attention for their outstanding lactation traits. Lactation, a complex physiological activity, is modulated by multiple factors. This study utilized high-throughput sequencing to conduct whole-transcriptome sequencing analysis on the mammary gland tissue of eight Kazakh mares, of which four were pregnant and four were non-pregnant, to systematically reveal the molecular regulatory mechanisms. The results showed differential expression in 2136 mRNAs, 180 lncRNAs, 104 miRNAs, and 1162 circRNAs. Gene ontology functional annotation indicates that these differentially expressed genes are involved in multiple key biological processes, such as the cellular process (BP), metabolic process, and biological regulation. Kyoto Encyclopedia of Genes and Genomes analysis suggests that the differentially expressed genes are significantly enriched in essential pathways such as cytokine–cytokine receptor interaction, the chemokine signaling pathway, and the PI3K-Akt signaling pathway. Additionally, this study constructed a competing endogenous RNA (ceRNA) regulatory network based on the differentially expressed genes (|log₂FC| > 1, FDR < 0.05), offering a novel perspective for revealing the functional regulation of the mammary gland. This study compared genomic differences in mammary gland tissue of pregnant and non-pregnant Kazakh mares and identified candidate genes that are closely related to lactation regulation. It found that various genes, such as PIK3CG, IL7R, and SOD2, play central regulatory roles in activating mammary gland functions. These findings provide theoretical support for explaining the molecular mechanisms underlying the mammary gland development of Kazakh mares. Full article

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancer types due to its late diagnosis, low survival rates, and high frequency of metastasis. Considering the molecular mechanism of PDAC development has not been fully elucidated, this study aimed to shed more light on the molecular regulatory signatures of circular RNAs (circRNAs) in PDAC progression and provide a different perspective to identify potential biomarkers as well as discover candidate repositioned drug molecules for the prevention or treatment of PDAC with network-based integrative analysis. The mRNA, miRNA, and circRNA expression profiles of PDAC were obtained from nine microarray datasets. Differentially expressed genes (DEGs), microRNAs (DEmiRNAs), and circular RNAs (DEcircRNAs) were identified. The competing endogenous RNA (ceRNA; DEG–DEmiRNA–DEcircRNA) regulatory network was constructed, which included 12 DEcircRNAs, 64 DEGs, and 6 miRNAs specific to PDAC. The ADAM12, MET, QKI, SEC23A, and ZEB2 were identified as hub genes and demonstrated significant survival probability for PDAC. In addition to providing novel biomarkers for diagnosis that can be detected non-invasively, the secretion levels of hub genes-associated proteins were found in plasma, serum, and oral epithelium. The drug repositioning analysis revealed vorinostat, meclocycline sulfosalicylate, and trichostatin A, which exhibited significant binding affinities to the hub genes compared to their inhibitors via molecular docking analysis. Full article

Atherosclerosis, a chronic inflammatory disease driving cardiovascular events, involves complex molecular networks where long non-coding RNAs (lncRNAs) are key regulators. This review synthesizes current knowledge on lncRNA Growth Arrest-Specific 5 (GAS5) in atherosclerosis, covering its expression, multifaceted roles in vascular cells, and molecular mechanisms. GAS5 is significantly upregulated in atherosclerotic plaques, exerting complex, cell-specific effects on vascular smooth muscle cells, macrophages, and endothelial cells. GAS5 modulates crucial pathophysiological processes like cell proliferation, apoptosis, inflammation, lipid metabolism, and foam cell formation, primarily by acting as a competing endogenous RNA (ceRNA) and through direct protein interactions. While promising as a biomarker, circulating GAS5 levels require further validation. Therapeutic strategies targeting GAS5, including antisense oligonucleotides (ASO) and small-molecule compounds, are under investigation. In conclusion, lncRNA GAS5 is a critical regulatory node in atherosclerosis pathobiology, offering significant opportunities for novel diagnostic and therapeutic interventions. Further research is vital to elucidate its intricate roles and translate these findings into clinical applications for atherosclerotic cardiovascular disease. Full article

The yak is a classic grazing livestock species on the Qinghai–Tibet Plateau, and fat deposition is indispensable for its survival and metabolism. Coding and non-coding RNAs (ncRNAs) play an important role in regulating fat deposition in livestock. In this study, the expression of mRNAs, lncRNAs, miRNAs, and circRNAs in the subcutaneous fat of yaks under grazing and stall feeding was measured using whole-transcriptome sequencing technology. A total of 677 differentially expressed (DE) mRNAs, 120 DE lncRNAs, 2216 DE circRNAs, and 15 DE miRNAs were identified, and their biological function was explored using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Co-expression RNA (ceRNA) networks between DE ncRNAs and DE mRNAs were further constructed, and the crucial RNAs and signal pathways regulating fat deposition in yaks were obtained. The effect of mRNAs and ncRNAs on fat deposition in yaks mainly depended on the PPAR, PI3K–Akt, and cAMP signaling pathways, and the regulatory pathways TCONS00042948, TCONS00012083/bta-miR-2316/MCAT, and NR4A3 may be critical in this process. This study provides some theoretical basis for breeding yak species and promotes improvements in yak production. Full article

The objective of this study is to investigate the molecular regulatory mechanisms of non-coding RNA (ncRNA) during the developmental process of multi-litter sheep ovaries and identify key regulatory genes that enhance the reproductive capacity of sheep. This study selected Small-Tail Han sheep (multi-litter sheep) and Ujumuqin sheep (single-litter sheep) as comparative models, constructed the expression profiles of ncRNAs and mRNAs in ovarian tissues, identified differentially expressed (DE) lncRNAs, circRNAs, miRNAs, and mRNAs, and performed target gene prediction along with functional and signaling pathway enrichment analyses. Reproduction-related pathways were further screened to construct competing endogenous RNA (ceRNA) regulatory networks (lncRNA–miRNA–mRNA and circRNA–miRNA–mRNA). Finally, the dual-luciferase reporter gene assay system was employed to perform the functional validation of the relevant targeted regulatory effects. A comprehensive screening identified 411 DE lncRNAs, 322 DE circRNAs, 26 DE miRNAs, and 29 DEGs from the ovarian tissues of Ujumqin and Small-Tail Han sheep. The results of the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses demonstrated that the DE target genes were significantly enriched in pathways associated with cell dedifferentiation, the positive regulation of embryonic development, glycosaminoglycan biosynthesis, Hippo signaling, and other signaling pathways. To identify genes associated with reproductive processes, we performed differential expression screening followed by pathway enrichment analysis, which revealed significant enrichment in reproductive regulatory pathways. Based on these findings, we constructed a ceRNA regulatory network incorporating 22 DEGs, 17 DE lncRNAs, three DE circRNAs, and one DE miRNA. Our analysis revealed that oar-let-7a is involved in signaling pathways such as oocyte meiosis and Hippo, suggesting it may serve as a key miRNA regulating the trait of multiple offspring. The dual-luciferase reporter assay was employed to confirm that oar-let-7a directly targets and regulates the expression of CPEB1. Additionally, it was demonstrated that circRNA803 and lncRNA MSTRG.19726 function as molecular sponges to competitively bind and regulate oar-let-7a. These findings suggest that oar-let-7a mediates the expression of CPEB1 via circRNA803 and lncRNA MSTRG.19726 sponge adsorption, thereby regulating the process of follicular dominance in sheep. The qRT-PCR method was employed to validate the expression patterns of nine randomly selected DEGs, and the results corroborated the reliability of the RNA-seq sequencing data. This study investigated the coordinated regulatory mechanism of DE ncRNAs and their corresponding target genes, identifying a ceRNA network, circRNA803/lncRNA MSTRG.19726-oar-let-7a-CPEB1, which plays a critical role in regulating the process of follicular dominance in sheep. These findings provide fundamental data for uncovering the reproductive potential of sheep and facilitate a comprehensive understanding of their reproductive characteristics, which hold significant guiding implications for enhancing reproductive efficiency. Full article

Circular RNAs (circRNAs), a class of covalently closed non-coding RNAs, are pivotal regulators of gene expression and contributors to disease pathogenesis. This study elucidated the biogenesis, functional significance, and regulatory network of circRNA_4083, a novel exon-derived circRNA originating from exons 22 and 23 of the MSH3 gene in chicken. Through comprehensive molecular characterization—including Sanger sequencing, RNase R digestion assays, and subcellular localization—we confirmed the robust stability and predominant cytoplasmic localization of circRNA_4083 across diverse chicken tissues. Mechanistic investigations revealed that reverse complementary sequences within flanking intronic regions are indispensable for its circularization, as demonstrated by overexpression plasmids (#1–#4) in DF-1 cells. Functional analyses demonstrated that circRNA_4083 significantly inhibited cell apoptosis and increased cellular viability. Integrative bioinformatics approaches predicted a competing endogenous RNA (ceRNA) network comprising 12 miRNAs and 2132 target genes (FDR < 0.05), with significant enrichment in pathways critical to genomic stability, including non-homologous end joining (NHEJ) and ubiquitin-mediated proteolysis. These findings position circRNA_4083 as a key modulator of cellular viability and genomic integrity, with potential implications for avian leukosis virus-J (ALV-J) pathogenesis and resistance breeding strategies. This work advances our understanding of circRNA-driven regulatory mechanisms in avian species and underscores their relevance in poultry health. Full article

Background/Objectives: Competing endogenous RNAs (ceRNA) are molecules that compete for the binding to a microRNA (miR). Usually, there are two ceRNA, one of which is a protein-coding RNA (mRNA), with the other being a long non-coding RNA (lncRNA). The miR role is to inhibit mRNA expression, either promoting its degradation or impairing its translation. The lncRNA can “sponge” the miR, thus impeding its inhibitory action on the mRNA. In their easier configuration, these three molecules constitute a regulatory axis for protein expression. However, each RNA can interact with multiple targets, creating branched and intersected axes that, all together, constitute what is known as a competing endogenous RNA network (ceRNET). Methods: In this systematic review, we collected all available data from PubMed about experimentally verified (by luciferase assay) regulatory axes in endometrial cancer (EC), excluding works not using this test; Results: This search allowed the selection of 172 bibliographic sources, and manually building a series of ceRNETs of variable complexity showed the known axes and the deduced intersections. The main limitation of this search is the highly stringent selection criteria, possibly leading to an underestimation of the complexity of the networks identified. However, this work allows us not only to hypothesize possible gap fillings but also to set the basis to instruct artificial intelligence, using adequate prompts, to expand the EC ceRNET by comparing it with ceRNETs of other cancers. Moreover, these networks can be used to inform and guide research toward specific, though still unidentified, axes in EC, to complete parts of the network that are only partially described, or even to integrate low complexity subnetworks into larger more complex ones. Filling the gaps among the existing EC ceRNET will allow physicians to hypothesize new therapeutic strategies that may either potentiate or substitute existing ones. Conclusions: These ceRNETs allow us to easily visualize long-distance interactions, thus helping to select the best treatment, depending on the molecular profile of each patient, for personalized medicine. This would yield higher efficiency rates and lower toxicity levels, both of which are extremely relevant factors not only for patients’ wellbeing, but also for the legal, regulatory, and ethical aspects of miR-based innovative treatments and personalized medicine as a whole. This systematic review has been registered in PROSPERO (ID: PROSPERO 2025 CRD420251035222). Full article

Prostate cancer (PCa) is the most frequently diagnosed malignancy in the male genitourinary tract. However, the regulatory mechanism of competitive endogenous RNAs (ceRNAs) in PCa remains unclear. In this study, we first performed immune scores of mRNA data from 481 PCa samples using single-sample Gene Set Enrichment Analysis (ssGSEA). Based on the immune scores, we then evaluated the tumor immune microenvironment and analyzed 28 types of immune cells in PCa, we constructed a comprehensive network with four lncRNAs (MEG3, PCAT1, SNHG19, TRG-AS1), three miRNAs (hsa-miR-488-3p, hsa-miR-210-5p, hsa-miR-137), and twenty-seven mRNAs (including H2AFJ, THBS1, HPGD). Among the 28 immune cell types, seven immune cell types were found to be significantly associated with clinical characteristics. These network nodes have prognostic significance in multiple cancers and play critical roles in malignancy development, indicating the network’s predictive capability. We also observed a strong correlation (r = 0.6) between T-helper type 1 (Th1) cells and lncRNA network modules. The network connectivity highlights the association between immune therapy biomarkers for PCa, particularly those related to H2AFJ, THBS1, and HPGD. These findings provide valuable insights into the ceRNA regulatory network and its implications for immune-based therapies in PCa. Full article

Objectives: This research aims to explore the therapeutic potential of Bi-Qi capsules in the treatment of gout by identifying crucial drug targets through a multidimensional data analysis strategy. Methods: Bi-Qi capsule drug targets and differentially expressed genes (DEGs) of gout were derived from public databases, such as Swiss Target Prediction, STITCH, and the GEO database. Subsequently, the overlapped targets were analyzed to elucidate the potential therapeutic mechanism and to identify candidate targets of Bi-Qi capsules against gout. Next, Mendelian randomization (MR) analysis was employed to screen and explore the causal relationship between candidate targets and gout. Finally, single-cell RNA sequencing (scRNA-seq), gene set enrichment analysis (GSEA), transcription factor and ceRNA regulatory networks, and molecular docking were performed to validate the role of the crucial targets of Bi-Qi capsules in the treatment of gout. Results: A total of 46 candidate targets were identified, in which KCNA5, PTGS2, and TNF exhibited significant causal relationships with gout (p < 0.05) and were regarded as the crucial targets. Through scRNA-seq and gene labeling, crucial targets were found to be expressed in eighteen cell clusters and eight cell types, which are closely associated with carbohydrate metabolism, nerve conduction, and the innate immunity process. Bi-Qi capsule active compounds such as tanshinone IIA, strychnine, tanshinaldehyde, cryptotanshinone, tumulosic acid, and glycyrrhetic acid exhibit a better binding ability to crucial targets. Conclusions: The results not only elucidate the anti-gout mechanism of Bi-Qi capsules but also provide an insight into multi-target natural medication for metabolic disease treatment, which contributes to guiding the clinical application of Bi-Qi capsules in the future. Full article

Intramuscular fat (IMF), or marbling, is a critical indicator of goat meat quality. Non-coding RNAs play a key role in the formation and deposition of IMF in vertebrates by regulating genes involved in its synthesis, degradation, and transport. The competing endogenous RNA (ceRNA) hypothesis identifies circular RNAs (circRNAs) as natural “sponges” for microRNAs (miRNAs). However, the precise mechanisms of circRNAs in goat IMF remain poorly understood. In the current study, we utilized existing sequencing data to construct a ceRNA regulatory network associated with intramuscular adipogenesis and fat deposition in goats. Our goal was to elucidate the post-transcriptional regulatory mechanism of family with sequence similarity 49 member B (FAM49B). Functionally, FAM49B was found to inhibit the differentiation of intramuscular preadipocytes and to directly interact with miR-27a-5p. Mechanistically, dual-luciferase reporter assays and quantitative real-time PCR (qRT-PCR) confirmed the interaction between circ0011446 and miR-27a-5p. Circ0011446 enhanced the expression of FAM49B mRNA and protein through post-transcriptional regulation. As a ceRNA, circ0011446 competitively binds miR-27a-5p, preventing miR-27a-5p from degrading FAM49B. In conclusion, our findings demonstrate that circ0011446 suppresses goat adipogenic differentiation of intramuscular preadipocytes by regulating the expression of the downstream target gene FAM49B through miR-27a-5p sequestration. This study provides a reference for goat meat quality or livestock breeding. Full article

Sweetpotato is the seventh largest crop worldwide, and soil salinization is a major environmental stress limiting its yield. Recent studies have shown that noncoding RNAs (ncRNAs) play important regulatory roles in plant responses to abiotic stress. However, ncRNAs in sweetpotato remain largely unexplored. This study analyzed the characteristics of salt-responsive ncRNAs in sweetpotato adventitious roots under salt stress via whole-transcriptome RNA sequencing. The results revealed that 3175 messenger RNAs (mRNAs), 458 microRNAs (miRNAs), 544 long-chain ncRNAs (lncRNAs), and 23 circular RNAs (circRNAs) were differentially expressed. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that most differentially expressed mRNAs (DEmRNAs) and miRNAs (DEmiRNAs) were enriched primarily in phenylpropanoid biosynthesis, starch and sucrose metabolism, the Mitogen-Activated Protein Kinase (MAPK) signaling pathway, plant hormone signal transduction, the mRNA surveillance pathway, and ATP-binding cassette (ABC) transporters. Gene Ontology (GO) enrichment analysis revealed that the majority of DEmRNAs, their target DEmiRNAs, and differentially expressed lncRNAs (DElncRNAs) were associated with the cell wall, oxidation–reduction, the plasma membrane, protein phosphorylation, metabolic processes, transcription factor activity, and the regulation of transcription. Additionally, based on the competitive endogenous RNA (ceRNA) hypothesis, we predicted interactions among different RNAs and constructed a salt-responsive ceRNA network comprising 22 DEmiRNAs, 42 DEmRNAs, 27 DElncRNAs, and 10 differentially expressed circRNAs (DEcircRNAs). Some miRNAs, such as miR408, miR169, miR160, miR5139, miR5368, and miR6179, were central to the network, suggesting their crucial roles in the sweetpotato salt response. Our findings provide a foundation for further research into the potential functions of ncRNAs and offer new targets for salt stress resistance improvement through the manipulation of ncRNAs. Full article

Exosomes are nanoscale vesicles secreted by cells that play vital regulatory roles in intercellular communication and immune responses. Listeria monocytogenes (L. Monocytogenes, LM) is a notable Gram-positive intracellular parasitic bacterium that infects humans and diverse animal species. However, the specific biological function of exosomes secreted by macrophages during L. Monocytogenes infection (hereafter EXO-LM) remains elusive. Here, we discovered that EXO-LM stimulated the secretion of inflammation-associated cytokines by macrophages, facilitating the intracellular survival of L. monocytogenes within macrophages. Transcriptomic analysis shows that EXO-LM significantly upregulates immune recognition and inflammation-related signaling pathways in macrophages. Furthermore, a ceRNA regulatory network comprising exosomal ncRNAs and macrophage RNAs was constructed through EXO-LM transcriptome sequencing. Utilizing bioinformatics and dual-luciferase reporter assays, we identified two potential binding sites between lncRNA Rpl13a-213 and miR-132-3p. Cell transfection experiments demonstrated that Rpl13a-213 overexpression augmented pro-inflammatory cytokine expression in macrophages, in contrast to the suppression by miR-132-3p overexpression. The decrease in Rpl13a-213 upon EXO-LM stimulation enhances miR-132-3p expression, dampening the inflammatory response in macrophages and aiding L. monocytogenes intracellular survival. This study unveils the immunomodulatory function of exosomal ncRNAs originating from macrophages, which provides fresh perspectives into the mechanisms underlying macrophage inflammatory response regulation by L. monocytogenes-infected cell-derived exosomes. Full article

Excessive deposition of abdominal fat will cause a waste of resources. In order to explore the key miRNAs and circRNA/lncRNA-miRNA-mRNA ceRNA regulatory network involved in regulating abdominal fat deposition, hematoxylin and eosin (H&E) staining was performed on abdominal fat tissues of ducks in the high abdominal fat rate group (HF) and low abdominal fat rate group (LF) at 21 and 42 days of age, and whole transcriptome sequencing was performed on abdominal tissues of ducks in the HF and LF groups at 42 days of age. The results showed that the number of adipocytes in ducks in the HF group was significantly higher than that in the LF group at 21 days of age (p < 0.001), while the number of adipocytes in ducks in the HF group at 42 days of age was significantly lower than that in the LF group (p < 0.001). In addition, transcriptome sequencing screened out a total of 14 differentially expressed miRNAs (10 miRNAs were significantly up-regulated, and 4 miRNAs were significantly down-regulated). By predicting the target genes of these differentially expressed miRNAs, a total of 305 target genes were obtained. Further analysis of miRNA target genes using GO and KEGG functional enrichment analyses revealed that these target genes were significantly enriched in the GnRH signaling pathway, the PPAR signaling pathway, insulin resistance, the mTOR signaling pathway, the AMPK signaling pathway, the FoxO signaling pathway, and other pathways related to adipose development. In addition, miRNA-205-x, miRNA-6529-x, miRNA-194-x, miRNA-215-x, miRNA-3074-x, miRNA-2954-x, novel-m0133-3p, and novel-m0156-5p were found to be important candidate miRNAs for abdominal fat deposition in ducks. These miRNAs were related to the expression of FOXO3, LIFR, Pdk4, PPARA, FBN1, MYH10, Cd44, PRELP, Esrrg, AKT3, and STC2. Based on these eight candidate miRNAs, a ceRNA regulatory network of circRNA/lncRNA-miRNA-mRNA regulating abdominal fat deposition was successfully constructed. The results of this study will provide a useful reference for accelerating the understanding of the molecular mechanism of duck abdominal fat deposition. Full article

Background/Objectives: Bone metastasis is a common and severe complication of lung adenocarcinoma (LUAD), impacting prognosis and treatment outcomes. Understanding the molecular mechanisms behind LUAD bone metastasis (LUADBM) is essential for developing new therapeutic strategies. The interactions between long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and mRNAs in the competing endogenous RNA (ceRNA) network are crucial in cancer progression and metastasis, but the regulatory mechanisms in LUADBM remain unclear. Methods: Microarray analysis was performed on clinical samples, followed by weighted gene co-expression network analysis (WGCNA) and construction of a ceRNA network. Molecular mechanisms were validated using colony formation assays, transwell migration assays, wound healing assays to assess cell migration, and osteoclastogenesis assays to evaluate osteoclast differentiation. Potential therapeutic drugs and their binding affinities were predicted using the CMap database and K_deep. The interaction between the small-molecule drug and its target protein was confirmed by surface plasmon resonance (SPR) and drug affinity responsive target stability (DARTS) assays. Mechanistic insights and therapeutic efficacy were further validated using patient-derived organoid (PDO) cultures, drug sensitivity assays, and in vivo drug treatments. Results: Our results identified the XLOC_006941/hsa-miR-543/NPRL3 axis as a key regulatory pathway in LUADBM. We also demonstrated that GATA3-driven Th2 cell infiltration creates an immunosuppressive microenvironment that promotes metastasis. Additionally, we confirmed that the inhibitor E7449 effectively targets NPRL3, and its combination with the IL4R-blocking antibody dupilumab resulted in improved therapeutic outcomes in LUADBM. Conclusions: These findings offer new insights into the molecular mechanisms of LUADBM and highlight potential therapeutic targets, including the XLOC_006941/miR-543/NPRL3 axis and GATA3-driven Th2 cell infiltration. The dual-target therapy combining E7449 with dupilumab shows promise for improving patient outcomes in LUADBM, warranting further clinical evaluation. Full article