Bioinformatics identification and integrative analysis of ferroptosis-related key lncRNAs in patients with osteoarthritis.

Ferroptosis and dysregulation of long non-coding RNA (lncRNA) have been described to be strictly relevant to the pathogenesis of osteoarthritis (OA). However, the connection between ferroptosis and lncRNA in OA is poorly appreciated. Herein, we investigated the functional contribution of lncRNA markers correlated with the progression of human OA by comprehensive bioinformatics analysis of a panoramic network of competing endogenous RNA (ceRNA) based on ferroptosis-related genes (FRGs). FRGs-related competing endogenous RNA (ceRNA) networks were generated using differentially expressed genes based on OA-related whole transcriptome data from the Gene Expression Omnibus (GEO) database via starBase, miRTarBase, and miRWalk databases. The pivotal lncRNAs were ascertained by topological features (degree, betweenness, and closeness) and subceRNA networks were re-visualized. The expression difference of pivotal lncRNAs was verified by quantitative real-time polymerase chain reaction (qRT-PCR). The latent molecular mechanisms of the global ceRNA and subceRNA networks were uncovered by the R package clusterProfiler-based enrichment analysis. A total of 98 dysregulated lncRNA-miRNA-mRNA regulatory relationships were attained in the FRGs-related panoramic ceRNA network of OA, covering 26 mRNAs, 20 miRNAs, and 20 lncRNAs. Three lncRNAs (AC011511.5, AL358072.1, and C9orf139) were ascertained as the central lncRNAs in the panoramic ceRNA network. Functional ensemble analysis illustrated that both the panoramic ceRNA network and the subceRNA network were integrally affiliated with the immune-inflammatory response, oxygen homeostasis, and cell death (apoptosis, autophagy, and ferroptosis). Comprehensive bioinformatics analysis of the FRGs-related ceRNA network determined three molecular biomarkers of lncRNAs that might be affiliated with OA progression.

Yang T ，Yang G ，Wang G ，Jia D ，Xiong B ，Lu X ，Li Y ... -  《-》

Identification and characterization of the ferroptosis-related ceRNA network in irreversible pulpitis.

The role of ferroptosis in irreversible pulpitis (IP) remains unclear. The competing endogenous RNA (ceRNA) theory that has been widely investigated is rarely used studied in IP. Hub lncRNAs selected from a ceRNA network may provide a novel hypothesis for the interaction of ferroptosis and IP. Differentially expressed genes (DEGs) were intersected with 484 ferroptosis markers to identify differentially expressed ferroptosis-related genes (DE-FRGs). Functional analysis and protein-protein interaction (PPI) networks were constructed to reveal the functions of DE-FRGs. Then, coexpression analyses were conducted between DE-FRGs and DElncRNAs to define ferroptosis-related DElncRNAs (FR-DElncRNAs). Predictions of DE-FRG- and FR-DElncRNA-related miRNAs were obtained, and members of both groups were selected. Additionally, two ceRNA networks consisting of FR-DElncRNAs, miRNAs and DE-FRGs from upregulated and downregulated groups were built. Finally, the hub lncRNAs of the ceRNA networks were used for immuno-infiltration analysis and qPCR verification. According to the results of PCA and clustering analysis, 5 inflamed and 5 healthy pulp tissue samples were selected for analysis. The intersection of DEGs with 484 ferroptosis marker genes identified 72 DE-FRGs. The response to stimulus, cellular process, signaling, localization, and biological regulation pathways related to DE-FRGs were enriched. In total, 161 downregulated and 40 upregulated FR-DElncRNAs were chosen by coexpression analysis for further investigation. The MultimiR package and starBase were used to predict miRNAs of DE-FRGs and FR-DElncRNAs, respectively. The upregulated ceRNA network contained 2 FR-DElncRNAs (↑), 19 miRNAs (↓) and 22 DE-FRGs (↑). The downregulated network contained 44 FR-DElncRNAs (↓), 251 miRNAs (↑) and 10 DE-FRGs (↓). Six hub lncRNAs were identified based on the MCC method (LUCAT1 and AC106897.1 ↑; LINC00943, AL583810.1, AC068888.1, and AC125257.1↓). In addition, strong relationships between hub lncRNAs and immune cells were shown by immune infiltration analysis. Finally, validated by qPCR assays of the pulp tissue of IP patients, the expression levels in clinical samples were consistent with the microarray data. Two ceRNA networks were comprehensively constructed, and 6 hub lncRNAs were identified. These genes provide novel insights into the relationship between ferroptosis and IP. Intriguingly, the LINC00943/hsa-miR-29a-3p/PDK4 axis was deemed to be the key node in this network.

Xie Q ，Yu H ，Liu Z ，Zhou B ，Fang F ，Qiu W ，Wu H ... -  《Frontiers in Immunology》

Construction of a ceRNA network of regulated ferroptosis in doxorubicin-induced myocardial injury.

Ferroptosis and long-noncoding RNAs (lncRNAs) play crucial roles in doxorubicin (DOX)-induced myocardial injury (DIMI). Nevertheless, there is no research to construct competing endogenous RNAs (ceRNAs) network between lncRNAs and ferroptosis-related key gene. So our research was designed to screen ferroptosis-related genes from differentially expressed mRNAs in DIMI and construct lncRNAs regulated ferroptosis-related key gene ceRNAs network. The male mice were injected with DOX intraperitoneally to induce myocardial injury, myocardial injury was evaluated by hematoxylin and eosin (HE) staining, and ferroptosis-related protein-glutathione peroxidase 4 (GPx4) protein expression was detected. The differentially expressed lncRNAs and mRNAs were detected by microarray, and the ferroptosis-related genes were screened to construct a protein-protein associations (PPA) network, the highest maximal clique centrality (MCC) score gene were identified by Cytoscape software, miRNAs bound to key genes and lncRNAs bound to miRNAs were predicted; then, the obtained lncRNAs were intersected with differentially expressed lncRNAs detected by microarray. Finally, the lncRNA/miRNA/mRNA ceRNA network of the highest MCC score gene regulating ferroptosis in DIMI was constructed. The expressions of the key components in ceRNA network were detected by qRT-PCR. Compared with the control group, in the DOX group, myocardial enzymes and HE staining showed that myocardium structure was changed, and GPx4 protein expression was decreased. The differentially expressed 10,265 lncRNAs and 6,610 mRNAs in the DOX group were detected via microarray. Among them, 114 ferroptosis-related genes were obtained to construct PPA networks, and Becn1 was identified as the key gene. Finally, the ceRNA network including Becn1, three miRNAs and four lncRNAs was constructed by predicting data of the Starbase database. The relative expressions of these components in ceRNA net were up-regulated and consistent with microarray results. Based on the microarray detection results and bioinformatics analysis, we screened ferroptosis-related gene Becn1 and constructed the lncRNA/miRNA/mRNA ceRNA network of regulated ferroptosis in DIMI.

Ye H ，Li Y ，Li L ，Huang Y ，Wang J ，Gao Q ... -  《PeerJ》

Development of Ferroptosis-Associated ceRNA Network in Periodontitis.

Periodontitis is a chronic inflammatory illness that may lead to tooth loosening and even loss, and its pathogenesis is not fully understood. Ferroptosis is an iron-dependent, regulated cell death. The present study aims to find the key ferroptosis-related genes (FRGs) in periodontitis and develop an mRNA-miRNA-lncRNA network to deeply explore the pathogenesis of periodontitis. Data from the Gene Expression Omnibus (GEO) database and FerrDb database were downloaded to discover the differentially expressed mRNA, miRNA, and FRGs. Functional enrichment analysis was conducted for the differentially expressed FRGs (DE-FRGs), including gene ontology, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and protein-protein interaction (PPI) network analysis. Targetscan and miRtarbase were used to estimate the miRNAs that DE-FRGs may interact with, whilst StarBase v3.0 was used for lncRNA-miRNA interaction. Seven DE-FRGs were identified through differential expression analysis. Interleukin 1 beta (IL1B) interacted with XBP1 and MMP13 in the PPI network. After taking the intersection between DE-miRNAs and predicted miRNAs, a ceRNA network containing IL1B, has-miR-185, has-miR-204, has-miR-211, has-miR-4306, and 28 lncRNAs was established. Seven FRGs in periodontitis were identified, which might promote deeper understanding of ferroptosis in periodontitis.

Zhang C ，Xue P ，Ke J ，Cai Q ... -  《-》

A Long Noncoding RNA (lncRNA)-Associated Competing Endogenous RNA (ceRNA) Network Identifies Eight lncRNA Biomarkers in Patients with Osteoarthritis of the Knee.

Chen Y ，Lin Y ，Bai Y ，Cheng D ，Bi Z ... -  《MEDICAL SCIENCE MONITOR》