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Background/Aims: Long non-coding RNAs (lncRNAs) acting as competing endogenous RNAs (ceRNAs) play significant roles in the development of tumors, but the functions of specific lncRNAs and lncRNA-related ceRNA networks have not been fully elucidated for colon adenocarcinoma (COAD). In this study, we aimed to clarify the lncRNA-microRNA (miRNA)-mRNA ceRNA network and potential lncRNA biomarkers in COAD. Methods: We extracted data from The Cancer Genome Atlas (TCGA) and identified COAD-specific mRNAs, miRNAs, and lncRNAs. The biological processes in Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were analyzed for COAD-specific mRNAs. We then constructed a ceRNA network of COAD-specific mRNAs, miRNAs and lncRNAs and analyzed the correlation between expression patterns and clinical features of the lncRNAs involved. After identifying potential mRNA targets of 4 lncRNAs related to overall survival (OS), we conducted stepwise analysis of these targets through GO and KEGG. Using tissue samples from our own patients, we also verified certain analytical results using quantitative real-time PCR (qRT-PCR). Results: Data from 521 samples (480 tumor tissue and 41 adjacent non-tumor tissue samples) were extracted from TCGA. A total of 258 specific lncRNAs, 206 specific miRNAs, and 1467 specific mRNAs were identified (absolute log 2 [fold change] > 2, false discovery rate < 0.01). Analysis of KEGG revealed that specific mRNAs were enriched in cancer-related pathways. The ceRNA network was constructed with 64 lncRNAs, 18 miRNAs, and 42 mRNAs. Among these lncRNAs involved in the network, 3 lncRNAs (LINC00355, HULC, and IGF2-AS) were confirmed to be associated with certain clinical features and 4 lncRNAs (HOTAIR, LINC00355, KCNQ1OT1, and TSSC1-IT1) were found to be negatively linked to OS (log-rank p < 0.05). KEGG showed that the potential mRNA targets of these 4 lncRNAs may be concentrated in the MAPK pathway. Certain results were validated by qRT-PCR. Conclusion: This study providing novel insights into the lncRNA-miRNA-mRNA ceRNA network and reveals potential lncRNA biomarkers in COAD.

Primary ovarian insufficiency (POI) is a common condition leading to the pathological decline of ovarian function in women of reproductive age, resulting in amenorrhea, hypogonadism, and infertility. Biochemical premature ovarian insufficiency (bPOI) is an intermediate stage in the pathogenesis of POI in which the fertility of patients has been reduced. Previous studies suggest that granulosa cells (GCs) play an essential role in the pathogenesis of POI, but their pathogenetic mechanisms remain unclear. To further explore the potential pathophysiological mechanisms of GCs in POI, we constructed a molecular long non-coding RNA (lncRNA)-microRNA (miRNA)-messenger RNA (mRNA) network using GC expression data collected from biochemical premature ovarian failure (bPOI) patients in the GEO database. We discovered that the GCs of bPOI patients had differential expression of 131 mRNAs, 191 lncRNAs, and 28 miRNAs. By systematic network analysis, we identified six key genes, including SRSF1, PDIA5, NEURL1B, UNK, CELF2, and CFL2, and five hub miRNAs, namely hsa-miR-27a-3p, hsa-miR-24-3p, hsa-miR-22-3p, hsa-miR-129-5p, and hsa-miR-17-5p, and the results suggest that the expression of these key genes may be regulated by two hub miRNAs, hsa-miR-27a-3p and hsa-miR-17-5p. Additionally, a POI model in vitro was created to confirm the expression of a few important genes. In this study, we discovered a unique lncRNA-miRNA-mRNA network based on the ceRNA mechanism in bPOI for the first time, and we screened important associated molecules, providing a partial theoretical foundation to better understand the pathogenesis of POI.

Studies have shown that long noncoding RNAs (lncRNAs) make up the major proportion of the ceRNA network and can regulate gene expression by competitively binding to miRNAs. This reveals the existence of an RNA-miRNA regulatory pathway and is of great biological significance. CeRNAs, as competitive endogenous RNAs, have revealed a new mechanism of interaction between RNAs. Until now, the role of lncRNA-mediated ceRNAs in breast cancer and their regulatory mechanisms have been elucidated to some extent. In this study, comprehensive analysis of large-scale invasive breast cancer samples in TCGA were conducted to further explore the developmental mechanism of invasive breast cancer and the potential predictive markers for invasive breast cancer prognosis in the ceRNA network. Abnormal expression profiles of invasive breast cancer associated mRNAs, lncRNAs and miRNAs were obtained from the TCGA database. Through further alignment and prediction of target genes, an abnormal lncRNA-miRNA-mRNA ceRNA network was constructed for invasive breast cancer. Through the overall survival analysis, Identification prognostic bio-markers for invasive breast cancer patients. In addition, we used Cytoscape plug-in BinGo for the different mRNA performance functional cluster analysis. Differential analysis revealed that 1059 lncRNAs, 86 miRNAs, and 2138 mRNAs were significantly different in invasive breast cancer samples versus normal samples. Then we construct an abnormal lncRNA-miRNA-mRNA ceRNA network for invasive breast cancer, consisting of 90 DElncRNAs, 18 DEmiRNAs and 26 DEmRNAs.Further, 4 out of 90 lncRNAs, 3 out of 26 mRNAs, and 2 out of 18 miRNAs were useful as prognostic biomarkers for invasive breast cancer patients (P value < 0.05). It is worth noting that based on the ceRNA network, we found that the LINC00466-Hsa-mir-204- LINC00466-hsa-mir-204- axis was present in 9 RNAs associated with the prognosis of invasive breast cancer. This study provides an effective bioinformatics basis for further understanding of the molecular mechanism of invasive breast cancerand for predicting outcomes, which can guide the use of invasive breast cancerdrugs and subsequent related research.

β-Thalassemia is a chronic hemolytic anemia caused by mutations in the β-globin gene. Increasing studies have shown that circular RNA (circRNA) plays a key role in abnormal hematopoiesis. Circ₀001428 is formed by circularization of the beta-mannosidase gene. However, little is known about the biological function of circ₀001428 in β-thalassemia. Circ₀001428 was selected from two circRNA microarrays (GSE241141 and GSE196682) of β-thalassemia, and expression levels of circ₀001428, miR-32-3p, miR-325-3p, γ-globin, activating transcription factor 4 (ATF4) and B-cell lymphoma/leukemia 11 A (BCL11A) were validated in 30 patients with β-thalassemia and 30 healthy controls. Cell proliferation, apoptosis, cell cycle, and erythroid differentiation were evaluated using stable knockdown or overexpression of circ₀001428. Fluorescence in situ hybridization, dual-luciferase reporter, and Western blots were performed to confirm interactions between circ₀001428, miR-32-3p/miR-325-3p, and ATF4. Circ₀001428 was downregulated in β-thalassemia patients compared to controls, promoted cell proliferation, decreased cell apoptosis, and inhibited terminal erythroid differentiation and γ-globin production. Mechanistically, circ₀001428 functions as a sponge for miR-32-3p and miR-325-3p to promote ATF4 expression, thereby activating BCL11A expression. Additionally, rescue experiments confirmed that circ₀001428 regulated erythropoiesis and γ-globin expression via promoting the ATF4-BCL11A axis by binding with miR-32-3p/miR-325-3p. Our findings reveal, for the first time, the important role of circ₀001428 in regulating erythropoiesis and γ-globin expression in β-thalassemia. The circ₀001428/miR-32-3p and miR-325-3p/ATF4/BCL11A/γ-globin signaling pathway may be a potential therapeutic target in β-thalassemia, especially for fetal hemoglobin modulation.

Shipu Liu,1 Zijian Zhang2 1Department of Occupational Medicine and Clinical Toxicology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100020, People’s Republic of China; 2Department of Urology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100020, People’s Republic of ChinaCorrespondence: Zijian Zhang, Department of Urology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, People’s Republic of China, Email zzhang742@uwalumni.comIntroduction: Emerging research emphasizes the critical role of local microbiota in shaping the tumor microenvironment (TME) and influencing cancer progression. Lung adenocarcinoma (LUAD) is distinguished by unique bacterial communities that appear to regulate immune responses, gene expression, and patient outcomes.Methods: We compiled microbiome profiles from several cancer types—including LUAD, lung squamous cell carcinoma (LUSC), breast carcinoma (BRCA), and thyroid carcinoma (THCA)—using public databases. Non-negative matrix factorization (NMF) was employed to categorize LUAD cases based on TME features, while DESeq2 was used to pinpoint bacterial taxa with differing abundance. Multi-omics networks were developed to integrate microbial, transcriptomic, and clinical data. For in vitro verification, we conducted siRNA-mediated knockdown of the long non-coding RNA LCIIAR and ISG15 in Lewis lung carcinoma cells, followed by proliferation assays.Results: In contrast to LUSC, BRCA, and THCA, LUAD exhibited distinct microbial populations, with notable enrichment of Cylindrospermopsis, Cyanothece, and Sulfolobus. NMF clustering identified two LUAD subtypes with differing prognoses. One longer survival cluster, marked by reduced bacterial presence and stronger antitumor immunity—reflected in stronger immune response, increased effector T cells activity, and greater immune cell infiltration. A competing endogenous RNA (ceRNA) network analysis established a link between LCIIAR and ISG15, both overexpressed in LUAD and associated with worse survival outcomes. Knockdown LCIIAR or ISG15 through siRNA significantly inhibited lung cancer cell proliferation, pointing to their roles in tumor growth and ceRNA-mediated regulation.Conclusion: LUAD features a distinctive microbiota that engages with inflammatory and ceRNA regulatory pathways. These observations underscore the value of targeting microbiome-influenced mechanisms, such as the LCIIAR–ISG15 axis, as a promising approach to enhance treatment outcomes in lung adenocarcinoma.Keywords: lung adenocarcinoma, microbiota, tumor microenvironment, ceRNA network

Protein aggregation is classically considered the main cause of neuronal death in neurodegenerative diseases (NDDs). However, increasing evidence suggests that alteration of RNA metabolism is a key factor in the etiopathogenesis of these complex disorders. Non-coding RNAs are the major contributor to the human transcriptome and are particularly abundant in the central nervous system, where they have been proposed to be involved in the onset and development of NDDs. Interestingly, some ncRNAs (such as lncRNAs, circRNAs and pseudogenes) share a common functionality in their ability to regulate gene expression by modulating miRNAs in a phenomenon known as the competing endogenous RNA mechanism. Moreover, ncRNAs are found in body fluids where their presence and concentration could serve as potential non-invasive biomarkers of NDDs. In this review, we summarize the ceRNA networks described in Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, amyotrophic lateral sclerosis and spinocerebellar ataxia type 7, and discuss their potential as biomarkers of these NDDs. Although numerous studies have been carried out, further research is needed to validate these complex interactions between RNAs and the alterations in RNA editing that could provide specific ceRNET profiles for neurodegenerative disorders, paving the way to a better understanding of these diseases.

[This corrects the article DOI: 10.3389/fmed.2025.1661259.].

Accumulating evidence shows that the abnormal increase in the mortality of intestinal epithelial cells (IECs) caused by apoptosis, pyroptosis, and necroptosis is closely related to the function of mucous membrane immunity and barrier function in patients with ulcerative colitis (UC). As a procedural death path that integrates the above-mentioned many deaths, the role of PANoptosis in UC has not been clarified. This study aims to explore the characterization of PANoptosis patterns and determine the potential biomarkers and therapeutic targets. We constructed a PANoptosis gene set and revealed significant activation of PANoptosis in UC patients based on multiple transcriptome profiles of intestinal mucosal biopsies from the GEO database. Comprehensive bioinformatics analysis revealed five key genes (ZBP1, AIM2, CASP1/8, IRF1) of PANoptosome with good diagnostic value and were highly correlated with an increase in pro-inflammatory immune cells and factors. In addition, we established a reliable ceRNA regulatory network of PANoptosis and predicted three potential small-molecule drugs sharing calcium channel blockers that were identified, among which flunarizine exhibited the highest correlation with a high binding affinity to the targets. Finally, we used the DSS-induced colitis model to validate our findings. This study identifies key genes of PANoptosis associated with UC development and hypothesizes that IRF1 as a TF promotes PANoptosome multicomponent expression, activates PANoptosis, and then induces IECs excessive death.

Long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) contribute to the onset of many neoplasias through RNA-RNA competitive interactions; in addition, they could be secreted by cancer cells into biological fluids, suggesting their potential diagnostic application. By analyzing the expression of 17 lncRNAs and 31 circRNAs in biopsies and serum exosomes from colorectal cancer (CRC) patients through qRT-PCR, we detected CCAT1, CCAT2, HOTAIR, and UCA1 upregulation and CDR1AS, MALAT1, and TUG1 downregulation in biopsies. In serum exosomes, UCA1 was downregulated, while circHIPK3 and TUG1 were upregulated. Combined receiver operating characteristic (ROC) curves of TUG1:UCA1 and circHIPK3:UCA1 showed high values of sensitivity and specificity. Through in vitro (i.e., RNA silencing and mitogen-activated protein kinase [MAPK] inhibition) and in silico analyses (i.e., expression correlation and RNA-RNA-binding prediction), we found that UCA1 could (1) be controlled by MAPKs through CEBPB; (2) sequester miR-135a, miR-143, miR-214, and miR-1271, protecting ANLN, BIRC5, IPO7, KIF2A, and KIF23 from microRNA (miRNA)-induced degradation; and (3) interact with mRNA 3′-UTRs, preventing miRNA binding. UCA1 and its co-regulated antisense LINC01764 could interact and reciprocally mask their own miRNA-binding sites. Functional enrichment analysis of the RNA-RNA network controlled by UCA1 suggested its potential involvement in cellular migration. The UCA1 regulatory axis would represent a promising target to develop innovative RNA-based therapeutics against CRC. [Display omitted]

Background Kawasaki disease (KD) is a febrile systemic vasculitis involvingchildren younger than five years old. However, the specific biomarkers and precise mechanisms of this disease are not fully understood, which can delay the best treatment time, hence, this study aimed to detect the potential biomarkers and pathophysiological process of KD through bioinformatic analysis. Methods The Gene Expression Omnibus database (GEO) was the source of the RNA sequencing data from KD patients. Differential expressed genes (DEGs) were screened between KD patients and healthy controls (HCs) with the “ limma ” R package. Weighted gene correlation network analysis (WGCNA) was performed to discover the most corresponding module and hub genes of KD. The node genes were obtained by the combination of the least absolute shrinkage and selection operator (LASSO) regression model with the top 5 genes from five algorithms in CytoHubba, which were further validated with the receiver operating characteristic curve (ROC curve). CIBERSORTx was employed to discover the constitution of immune cells in KDs and HCs. Functional enrichment analysis was performed to understand the biological implications of the modular genes. Finally, competing endogenous RNAs (ceRNA) networks of node genes were predicted using online databases. Results A total of 267 DEGs were analyzed between 153 KD patients and 92 HCs in the training set, spanning two modules according to WGCNA. The turquoise module was identified as the hub module, which was mainly enriched in cell activation involved in immune response, myeloid leukocyte activation, myeloid leukocyte mediated immunity, secretion and leukocyte mediated immunity biological processes; included type II diabetes mellitus, nicotinate and nicotinamide metabolism, O-glycan biosynthesis, glycerolipid and glutathione metabolism pathways. The node genes included ADM, ALPL, HK3, MMP9 and S100A12, and there was good performance in the validation studies. Immune cell infiltration analysis revealed that gamma delta T cells, monocytes, M0 macrophage, activated dendritic cells, activated mast cells and neutrophils were elevated in KD patients. Regarding the ceRNA networks, three intact networks were constructed: NEAT1/NORAD/XIST-hsa-miR-524-5p-ADM, NEAT1/NORAD/XIST-hsa-miR-204-5p-ALPL, NEAT1/NORAD/XIST-hsa-miR-524-5p/hsa-miR-204-5p-MMP9. Conclusion To conclude, the five-gene signature and three ceRNA networks constructed in our study are of great value in the early diagnosis of KD and might help to elucidate our understanding of KD at the RNA regulatory level.