The competing endogenous RNA (ceRNA) hypothesis is a new pattern of gene posttranscriptional regulation. Encoding mRNA, long noncoding RNA (lncRNA), pseudogene transcript, circular RNA (circRNA), etc. can regulate gene expression by binding microRNA (miRNA). According to the research, ceRNA regulatory network participates in the maintenance of normal physiological state, occurrence and development of diseases. This paper reviewed ceRNA with the following respects: the proposal of ceRNA hypothesis, members of ceRNA regulatory network, research status, limitations and future development directions of this hypothesis. It will contribute to clarify the pathogenesis of much diseases including tumor and provide a new strategy for the diagnosis and treatment of disease.
To evaluate the differential expression profiles of the lncRNAs, miRNAs, mRNAs and ceRNAs, and their implication in the prognosis in clear cell renal cell carcinoma (CCRCC), the large sample genomics analysis technologies were used in this study. The RNA and miRNA sequencing data of CCRCC were obtained from The Cancer Genome Atlas (TCGA) database, and R software was used for gene expression analysis and survival analysis. Cytoscape software was used to construct the ceRNA network. The results showed that a total of 1 570 lncRNAs, 54 miRNAs, and 17 mRNAs were differentially expressed in CCRCC, and most of their expression levels were up-regulated (false discovery rate < 0.01 and absolute log fold change > 2). The ceRNA regulatory network showed the interaction between 89 differentially expressed lncRNAs and 9 differentially expressed miRNAs. Further survival analysis revealed that 38 lncRNAs (including COL18A1-AS1, TCL6, LINC00475, UCA1, WT1-AS, HOTTIP, PVT1, etc.) and 2 miRNAs (including miR-21 and miR-155) were correlated with the overall survival time of CCRCC (P < 0.05). Together, this study provided us several new evidences for the targeted therapy and prognosis assessment of CCRCC.
ObjectiveTo detect the differentially expressed circular RNA (circRNA) in rotator cuff tendinopathy and analyze the potential molecular mechanism of these parental genes.MethodsTen supraspinatus tendons donated from patients who underwent tendon repair surgery between June 2018 and June 2019 were used for RNA-sequence. All rotator cuff tendinopathy and normal tendon samples were confirmed by MRI, histological staining, and observation by arthroscopy. All pathological tendons were matched with tendon samples for patients’ age, gender, body mass index, and Bonar score. The bioinformatic analysis was performed based on the differentially expressed circRNA and their parental genes, including gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and competing endogenous RNA (ceRNA) network construction.ResultsThere were 94 differentially expressed circRNAs, including 31 up-regulated and 63 down-regulated, detected between the rotator cuff tendinopathy and normal tendon samples with |log2 fold change (FC)| >2, P<0.05. GO analysis showed that the genes were mostly enriched in response to cyclic adenosine monophosphate (cAMP). KEGG pathway analysis showed that the most genes were enriched in extracellular matrix-receptor interaction, protein digestion and absorption, cell cycle, and nuclear factor κB signaling pathway. ceRNA networks showed the interactions among circRNAs, mRNAs, and miRNAs. And circRNA.8951-has-miR-6089-DNMT3B was the most sum max energy.ConclusionThis bioinformatic study reveals several potential therapeutic targets for rotator cuff tendinopathy, which paves the way to better treatment and prevention of this disorder.
Objective To explore the mode and role of differential expression of circular RNAs (circRNAs) in myelodysplastic syndrome (MDS). Methods We preprocessed and analyzed the circRNA expression profile datasets GSE163386, GSE94591, and GSE81173 in the GEO (Gene Expression Omnibus) database. By using the circBank database and the ENCORI, miRDB, and miRWalk databases to predict microRNAs (miRNAs) that interacted with differentially expressed circRNAs and messenger RNAs (mRNAs), the circRNA-miRNA-mRNA axis was constructed. We retrieved miRNAs related to MDS in PubMed and further obtained competing endogenous RNA (ceRNA) networks related to MDS by taking intersections. Results Through analysis, 128 differentially expressed circRNAs were identified, 48 highly expressed, and 80 low expressed. Among differentially expressed circRNAs with multiple differences>10, 3 were upregulated and 11 were downregulated. Through analysis, 101 differentially expressed mRNA were identified, with 9 upregulated and 92 downregulated. Intersecting with the MDS related miRNAs retrieved by PubMed, we further obtained the MDS related ceRNA network, namely circRNA (has_circ_0061137)-miRNA (has-miR-16-5p)-mRNA (RUBCNL, TBC1D9, SLC16A6) and circRNA (has_circ_0061137)-miRNA (has-miR-125b-5p)-mRNA (CCR5, SLC16A6, IRF4), all of which were downregulated. Conclusion The ceRNA networks revealed in this study may help elucidate the circRNA mechanism in MDS.
Objective A series of bioinformatics methods were used to identify ferroptosis related biomarkers in lupus nephritis (LN). Methods We retrieved sequencing data of GSE112943 from the GEO (Gene Expression Omnibus) database and screened LN differentially expressed genes. We searched for ferroptosis-related gene (FRG) through FerrDb database, and screened LN-FRG. We conducted enrichment analysis on the LN-FRGs using David online bioinformatics database and screened the core LN-FRG using cytoHubba. We used external data sets to verify the core LN-FRGs, constructed competing endogenous RNA networks, and conducted molecular docking analysis. Results A total of 37 LN-FRGs were selected through screening. These genes are mainly enriched in inflammation, immune regulation and ferroptosis related signaling pathways. Through the cytoHubba and external dataset validation, the key core LN-FRG of ATF3 (activating transcription factor 3) was ultimately identified, and its expression was significantly increased in LN (P<0.05). Molecular docking analysis showed that ATF3 was closely bound to SLC7A11 and NRF2, and may participate in the occurrence and development of LN through the microRNA-27-ATF3 regulation axis. Conclusion The pivotal gene ATF3 may participate in the inflammation and immune injury of LN through ferroptosis.
ObjectiveA competing endogenous RNA (ceRNA) regulatory network associated with long non-coding RNA (lncRNA) specific for lung adenocarcinoma (LUAD) was constructed based on bioinformatics methods, and the functional mechanism of actinfilament-associated protein 1-antisense RNA1 (AFAP1-AS1) in LUAD was analyzed, in order to provide a new direction for the study of LUAD therapeutic targets. MethodsThe gene chip of LUAD was downloaded from the Gene Expression Omnibus (GEO), and lncRNA and mRNA with differential expression between LUAD and normal tissues were screened using GEO2R online software, and their target genes were predicted by online databases to construct ceRNA networks and perform enrichment analysis. In cell experiments, AFAP1-AS1 was genetically knocked down and siRNA was constructed and transfected into LUAD cells A549 by cell transfection. CCK8, transwell, scratch assay and flow cytometry were used to detect the ability of cells to proliferate, invade, migrate and apoptosis. ResultsA total of 6 differentially expressed lncRNA and 494 differentially expressed mRNA were identified in the microarray of LUAD. The ceRNA network involved a total of 6 lncRNA, 22 miRNA, and 55 mRNA. Enrichment analysis revealed that mRNA was associated with cancer-related pathways. In cell assays, knockdown of AFAP1-AS1 inhibited cell proliferation, invasion, and migration, and AFAP1-AS1 promoted apoptosis. ConclusionIn this study, we construct a lncRNA-mediated ceRNA network, which may help to further investigate the mechanism of action of LUAD. In addition, through cellular experiments, AFAP1-AS1 is found to have potential as a therapeutic target for LUAD.