Regulatory Role of miRNAs and lncRNAs in Gout.

To explore the regulatory functions of ceRNA networks in the nosogenesis of gout and search for potential therapeutic targets. We searched the GEO database and downloaded the lncRNA microarray chipset GSE160170. This matrix series was analyzed to yield differentially expressed lncRNAs and mRNAs. Then, the correlations between lncRNAs and miRNAs were obtained by comparing the highly conserved miRNA families. The predicted miRNA-regulating mRNAs were matched to the differentially expressed mRNAs from the chipset analyses to obtain miRNA-mRNA interactions. Next, we used the Cytoscape software to model ceRNA networks and the STRING database to determine their protein-protein interactions. The R software was used to algorithmically screen the functional pathways of key PPI modules in the ceRNA networks. A total of 354 lncRNAs (140 downregulated and 214 upregulated) and 693 mRNAs (399 downregulated and 294 upregulated) were differentially expressed between the gout group and the healthy group. The ceRNA network of differentially expressed lncRNAs contained 86 lncRNAs (35 downregulated and 51 upregulated), 29 miRNAs, and 57 mRNAs. The processes identified in the GO enrichment analysis included gene transcription, RNA polymerase II transcription, and the regulation of cell growth and apoptosis. The pathways identified in the KEGG enrichment analysis included IL-17, TNF, and MAPK signaling. Nine lncRNAs (AC104024, AC084082, AC083843, FAM182A, AC022819, FAM215B, AP000525, TTTY10, and ZNF346-IT1), eleven miRNAs (hsa-miR-1297, hsa-miR-17-5p, hsa-miR-429, hsa-miR-139-5p, hsa-miR-449c-5p, hsa-miR-125a-5p, hsa-miR-125b-5p, hsa-miR-23b-3p, hsa-miR-217, hsa-miR-363-3p, and hsa-miR-20b-5p), and nine mRNAs (JUN, CASP2, PMAIP1, FOS, TNFAIP3, MAP3K8, BTG2, NR4A2, and DUSP2) were identified in the exploration of the key modules. Characterization of ceRNA networks could be a promising approach for better understanding the pathogenesis of gout, with the TTTY10/hsa-miR-139-5p/AP-1 axis likely to be of clinical significance.

Shu J ，Chen M ，Ya C ，Yang R ，Li F ... -  《-》

Construction of lncRNA-miRNA-mRNA network based on ceRNA mechanism reveals the function of lncRNA in the pathogenesis of gout.

To identify differentially expressed lncRNA, miRNA, and mRNA during the pathogenesis of gout, explore the ceRNA network regulatory mechanism of gout, and seek potential therapeutic targets. First, gout-related chips were retrieved by GEO database. Then, the analysis of differentially expressed lncRNAs and mRNAs was conducted by R language and other software. Besides, miRNA and its regulated mRNA were predicted based on public databases, the intersection of differentially expressed mRNA and predicated mRNA was taken, and the lncRNA-miRNA-mRNA regulatory relationships were obtained to construct the ceRNA regulatory network. Subsequently, hub genes were screened by the STRING database and Cytoscape software. Then the DAVID database was used to illustrate the gene functions and related pathways of hub genes and to mine key ceRNA networks. Three hundred and eighty-eight lncRNAs and 758 mRNAs were identified with significant differential expression in gout patient, which regulates hub genes in the ceRNA network, such as JUN, FOS, PTGS2, NR4A2, and TNFAIP3. In the ceRNA network, lncRNA competes with mRNA for miRNA, thus affecting the IL-17 signaling pathway, TNF signaling pathway, Oxytocin signaling pathway, and NF-κB signaling pathway through regulating the cell's response to chemical stress. The research indicates that five miRNAs (miR-429, miR-137, miR-139-5p, miR-217, miR-23b-3p) and five lncRNAs (SNHG1, FAM182A, SPAG5-AS1, HNF1A-AS1, UCA1) play an important role in the formation and development of gout. The interaction in the ceRNA network can affect the formation and development of gout by regulating the body's inflammatory response as well as proliferation, differentiation, and apoptosis of chondrocytes and osteoclasts. The identification of potential therapeutic targets and signaling pathways through ceRNA network can provide a reference for further research on the pathogenesis of gout.

Chen F ，Zhang X ，Chen Y ，Chai Y ，Jiang X ，Li H ... -  《-》

A ceRNA network of BBOX1-AS1-hsa-miR-125b-5p/hsa-miR-125a-5p-CDKN2A shows prognostic value in cervical cancer.

Cervical cancer (CC) ranks fourth most diagnosed cancer and cancer mortality in women. Long non-coding RNAs (lncRNAs) take important roles in CC development. This study aimed to identify more and novel competing endogenous RNA (ceRNA) mechanisms of lncRNAs in CC. The miRNA expression dataset GSE20592 and lncRNA/mRNA expression dataset GSE63514 were downloaded from Gene Expression Omnibus. The differentially expressed genes (DEGs), differentially expressed lncRNAs (DElncRNAs), and differentially expressed miRNAs (DEmiRNAs) between CC tumor and normal samples were identified with the criteria of adj.P.Value < 0.05 (Benjamini & Hochberg) and |log2(fold change)|>2. Functional enrichment analysis was performed for DEGs. The interaction pairs among lncRNAs, miRNAs and mRNAs were predicted and the ceRNA network was then constructed. Survival analysis was performed based on the TCGA dataset. Totally, 42 DEmiRNAs, 25 DElncRNAs, and 518 DEGs were identified in CC tumor samples versus normal tissues. The DEGs were associated with 'GO:0006260: DNA replication', 'GO:0051301: cell division', and 'hsa01100:Metabolic pathways'. The ceRNA network consisted of 878 lncRNA-miRNA-mRNA pairs. Of the miRNAs, lncRNAs, and genes with the top 10 interaction degrees in the ceRNA network, the upregulated cyclin dependent kinase inhibitor 2A gene (CDKN2A) was targeted by the downregulated DEmiRNAs including hsa-miR-125b-5p and hsa-miR-125a-5p, which were targeted by the upregulated DElncRNA BBOX1-AS1. The high expression level of CDKN2A contributed to the poor overall survival of patients with CC. The BBOX1-AS1-hsa-miR-125b-5p/hsa-miR-125a-5p-CDKN2A ceRNA network is of great value in CC development.

Wang T ，Zhang XD ，Hua KQ 《-》

Identification of a lncRNA/circRNA-miRNA-mRNA ceRNA Network in Alzheimer's Disease.

Su L ，Zhang Y ，Wang Y ，Wei H ... -  《Journal of Integrative Neuroscience》

Construction of Endometrial Carcinoma ceRNA Network and Screening of Key Genes Based on TCGA Database.

Long noncoding RNA (lncRNA) has received more and more attention in human tumor research. This study is aimed at clarifying the regulatory network of lncRNAs-microRNAs- (miRNAs-) mRNAs and at determining the relevant targets in the development of endometrial cancers. Download the miRNA, mRNA, and lncRNA expression profile data of endometrial cancer patients from TCGA; use the "DESeq2" package of R software to identify the differential expression of miRNAs, mRNAs, and lncRNAs; construct a network of ceRNA; and perform gene ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway enrichment assessment on mRNAs in the network of ceRNA; string and Cytoscape 3.7.2 perform PPI assessment on target genes and TOP 10 hub gene screening; Cytoscape 3.7.2 computer program was employed for constructing the lncRNA-miRNA-TOP10 hub mRNA network diagram to determine the signal axis; StarBase database to verify the Top10 hub mRNA expression; the "survival" package in R computer program was implemented to analyze the survival rate of all genes on the lncRNA-miRNA-Top10 hub mRNA network diagram; RT-qPCR to verify the expression level of genes on the signal axis. 1119 differential mRNAs, 14 differential lncRNAs, and 65 differential miRNAs were screened in TCGA; we constructed a ceRNA regulatory network composed of 5 DELs, 7 DEMs, and 90 DEGs; String combined with Cytoscape to screen out Top10 hub genes, namely: LEFTY1, LIN28A, LHX3, ST8SIA3, CEP55, FBXO32, DCN, ANGPTL1, ADRA1A, and KCNMA1; the StarBase database verification results show that ADRA1A, ANGPTL1, FBXO32, KCNMA1, and DCN are downregulated in endometrial cancer tissues; LEFTY1, LIN28A, LHX3, ST8SIA3, and CEP55 are upregulated in endometrial cancer; the constructed lncRNA-miRNA-hub Top10 mRNA network map identified CTD-2314B22, RP11-89 K21/hsa-miR-143, hsa-miR-424/LEFTY1, LIN28A, LHX3, ST8SIA3, and CEP55 signal axis; survival analysis results show that CTD-2314B22, RP11-89 K21, hsa-miR-96, hsa-miR-211, LHX3, ST8SIA3, and DCN are all related to survival; RT-qPCR results indicate CTD-2314B22, RP11-89 K21, LEFTY1, LIN28A, LHX3, ST8SIA3, and CEP55 are upregulated in endometrial cancer cells, and hsa-miR-143 and hsa-miR-424 are downregulated in endometrial cancer cells. From the perspective of the lncRNA-miRNA-mRNA network, our study identified CTD-2314B22, RP11-89 K21/hsa-miR-143, hsa-miR-424/LEFTY1, LIN28A, LHX3, ST8SIA3, and CEP55 signal axis, which can present considerably potent biomarkers and therapeutic targets for treating endometrial cancer.

Song Y ，Chu P ，Li P ，Li F ... -  《-》