Long non-coding RNA-associated competing endogenous RNA axes in the olfactory epithelium in schizophrenia: a bioinformatics analysis.
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ABSTRACT:
SUBMITTER: Sabaie H
PROVIDER: S-EPMC8718521 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Schizophrenia (SCZ) is a serious psychiatric condition with a 1% lifetime risk. SCZ is one of the top ten global causes of disabilities. Despite numerous attempts to understand the function of genetic factors in SCZ development, genetic components in SCZ pathophysiology remain unknown. The competing endogenous RNA (ceRNA) network has been demonstrated to be involved in the development of many kinds of diseases. The ceRNA hypothesis states that cross-talks between coding and non-coding RNAs, including long non-coding RNAs (lncRNAs), via miRNA complementary sequences known as miRNA response elements, creates a large regulatory network across the transcriptome. In the present study, we developed a lncRNA-related ceRNA network to elucidate molecular regulatory mechanisms involved in SCZ. Microarray datasets associated with brain regions (GSE53987) and lymphoblasts (LBs) derived from peripheral blood (sample set B from GSE73129) of SCZ patients and control subjects containing information about both mRNAs and lncRNAs were downloaded from the Gene Expression Omnibus database. The GSE53987 comprised 48 brain samples taken from SCZ patients (15 HPC: hippocampus, 15 BA46: Brodmann area 46, 18 STR: striatum) and 55 brain samples taken from control subjects (18 HPC, 19 BA46, 18 STR). The sample set B of GSE73129 comprised 30 LB samples (15 patients with SCZ and 15 controls). Differentially expressed mRNAs (DEmRNAs) and lncRNAs (DElncRNAs) were identified using the limma package of the R software. Using DIANA-LncBase, Human MicroRNA Disease Database (HMDD), and miRTarBase, the lncRNA- associated ceRNA network was generated. Pathway enrichment of DEmRNAs was performed using the Enrichr tool. We developed a protein-protein interaction network of DEmRNAs and identified the top five hub genes by the use of STRING and Cytoscape, respectively. Eventually, the hub genes, DElncRNAs, and predictive miRNAs were chosen to reconstruct the subceRNA networks. Our bioinformatics analysis showed that twelve key DEmRNAs, including BDNF, VEGFA, FGF2, FOS, CD44, SOX2, NRAS, SPARC, ZFP36, FGG, ELAVL1, and STARD13, participate in the ceRNA network in SCZ. We also identified DLX6-AS1, NEAT1, MINCR, LINC01094, DLGAP1-AS1, BABAM2-AS1, PAX8-AS1, ZFHX4-AS1, XIST, and MALAT1 as key DElncRNAs regulating the genes mentioned above. Furthermore, expression of 15 DEmRNAs (e.g., ADM and HLA-DRB1) and one DElncRNA (XIST) were changed in both the brain and LB, suggesting that they could be regarded as candidates for future biomarker studies. The study indicated that ceRNAs could be research candidates for investigating SCZ molecular pathways.
| S-EPMC8709859 | biostudies-literature
Project description:Multiple sclerosis (MS) is an immune-mediated demyelinating and degenerative disease with unknown etiology. Inappropriate response of T-cells to myelin antigens has an essential role in the pathophysiology of MS. The clinical and pathophysiological complications of MS necessitate identification of potential molecular targets to understand the pathogenic events of MS. Since the functions and regulatory mechanisms of long non-coding RNAs (lncRNAs) acting as competing endogenous RNAs (ceRNAs) in MS are yet uncertain, we conducted a bioinformatics analysis to explain the lncRNA-associated ceRNA axes to clarify molecular regulatory mechanisms involved in T-cells responses in MS. Two microarray datasets of peripheral blood T-cell from subjects with relapsing-remitting MS and matched controls containing data about miRNAs (GSE43590), mRNAs and lncRNAs (GSE43591) were downloaded from the Gene Expression Omnibus database. Differentially expressed miRNAs (DEmiRNAs), mRNAs (DEmRNAs), and lncRNAs (DElncRNAs) were identified by the limma package of the R software. Protein-protein interaction (PPI) network and module were developed using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) and the Molecular Complex Detection (MCODE) Cytoscape plugin, respectively. Using DIANA-LncBase and miRTarBase, the lncRNA-associated ceRNA axes was constructed. We conducted a Pearson correlation analysis and selected the positive correlations among the lncRNAs and mRNAs in the ceRNA axes. Lastly, DEmRNAs pathway enrichment was conducted by the Enrichr tool. A ceRNA regulatory relationship among Small nucleolar RNA host gene 1 (SNHG1), hsa-miR-197-3p, YOD1 deubiquitinase (YOD1) and zinc finger protein 101 (ZNF101) and downstream connected genes was identified. Pathway enrichment analysis showed that DEmRNAs were enriched in "Protein processing in endoplasmic reticulum" and "Herpes simplex virus 1 infection" pathways. To our knowledge, this would be the first report of a possible role of SNHG1/hsa-miR-197-3p/YOD1/ZNF101 axes in the pathogenesis of MS. This research remarks on the significance of ceRNAs and prepares new perceptions for discovering the molecular mechanism of MS.
| S-EPMC8696673 | biostudies-literature
Project description:Schizophrenia (SCZ) is a serious mental condition with an unknown cause. According to the reports, Brodmann Area 10 (BA10) is linked to the pathology and cortical dysfunction of SCZ, which demonstrates a number of replicated findings related to research on SCZ and the dysfunction in tasks requiring cognitive control in particular. Genetics' role in the pathophysiology of SCZ is still unclear. Therefore, it may be helpful to understand the effects of these changes on the onset and progression of SCZ to find novel mechanisms involved in the regulation of gene transcription. In order to determine the molecular regulatory mechanisms affecting the SCZ, the long non-coding RNA (lncRNA)-associated competing endogenous RNAs (ceRNAs) axes in the BA10 area were determined using a bioinformatics approach in the present work. A microarray dataset (GSE17612) consisted of brain post-mortem tissues of the BA10 area from SCZ patients and matched healthy subjects was downloaded from the Gene Expression Omnibus (GEO) database. This dataset included probes for both lncRNAs and mRNAs. Using the R software's limma package, the differentially expressed lncRNAs (DElncRNAs) and mRNAs (DEmRNAs) were found. The RNA interactions were also discovered using the DIANA-LncBase and miRTarBase databases. In the ceRNA network, positive correlations between DEmRNAs and DElncRNAs were evaluated using the Pearson correlation coefficient. Finally, lncRNA-associated ceRNA axes were built by using the co-expression and DElncRNA-miRNA-DEmRNA connections. We identified the DElncRNA-miRNA-DEmRNA axes, which included two key lncRNAs (PEG3-AS1, MIR570HG), seven key miRNAs (hsa-miR-124-3p, hsa-miR-17-5p, hsa-miR-181a-5p, hsa-miR-191-5p, hsa-miR-26a-5p, hsa-miR-29a-3p, hsa-miR-29b-3p), and eight key mRNAs (EGR1, ETV1, DUSP6, PLOD2, CD93, SERPINB9, ANGPTL4, TGFB2). Furthermore, DEmRNAs were found to be enriched in the "AGE-RAGE signaling pathway in diabetic complications", "Amoebiasis", "Transcriptional misregulation in cancer", "Human T-cell leukemia virus 1 infection", and "MAPK signaling pathway". This study offers research targets for examining significant molecular pathways connected to the pathogenesis of SCZ, even though the function of these ceRNA axes still needs to be investigated.
| S-EPMC9671706 | biostudies-literature
Project description:Background Adrenocortical carcinoma (ACC) is a malignant tumor with poor prognosis and unclear pathogenesis. This study aimed to explore the role of long non-coding RNAs (lncRNAs) in ACC. Methods We obtained the lncRNA expression profiles of 10 ACC samples and 6 normal control samples from the GEO database and identified differentially expressed RNAs using the limma package in R. Results We obtained a total of 391 differentially expressed lncRNAs (DElncRNAs) and 1,313 differentially expressed mRNAs (DEmRNAs) between ACC samples and normal control samples. Using Cytoscape v3.7.0, we then constructed a lncRNA-miRNA-mRNA (competing endogenous RNA, or ceRNA) network consisting of 87 lncRNAs, 31 miRNAs, and 78 mRNAs. Applying GO and KEGG enrichment analysis for 78 mRNAs in the ceRNA network, we identified 9 GO terms and 21 significantly enriched pathways. A PPI network was constructed using STRING online tools and Cytoscape v3.7.0, identifying 10 key genes. Finally, through Kaplan-Meier survival analysis, we identified five lncRNAs (LINC00887, MEIS1-AS2, MIR29B2CHG, MIR503HG, and SREBF2-AS1) associated with prognosis in patients with ACC. Conclusions In summary, we constructed a ceRNA network and propose a new method for lncRNA research in ACC. Our results provide new clues for further exploration of lncRNAs in the pathogenesis of ACC.
| S-EPMC8798464 | biostudies-literature
Project description:Gastric cancer (GC) is a common type of cancer, and identification of novel diagnostic biomarkers associated with this disease is important. The present study aimed to identify novel diagnostic biomarkers associated with the prognosis of GC, using an integrated bioinformatics approach. Differentially expressed long non-coding RNAs (lncRNAs) associated with GC were identified using Gene Expression Omnibus datasets (GSE58828, GSE72305 and GSE99416) and The Cancer Genome Atlas database. A competing endogenous RNA network that incorporated five lncRNAs [long intergenic non-protein coding RNA 501 (LINC00501), LINC00365, SOX21 antisense divergent transcript 1 (SOX21-AS1), GK intronic transcript 1 (GK-IT1) and DLEU7 antisense RNA 1 (DLEU7-AS1)], 29 microRNAs and 114 mRNAs was constructed. Gene Ontology and protein-protein interaction network analyses revealed that these lncRNAs may be involved in 'biological regulation', 'metabolic process', 'cell communication', 'developmental process', 'cell proliferation', 'reproduction' and the 'cell cycle'. The results of receiver operating characteristic curve analysis demonstrated that LINC00501 (AUC=0.819), LINC00365 (AUC=0.580), SOX21-AS1 (AUC=0.736), GK-IT1 (AUC=0.823) and DLEU7-AS1 (AUC=0.932) had the potential to become valuable diagnostic biomarkers for GC. Associations with clinicopathological characteristics demonstrated that LINC00501 expression was significantly associated with sex (P=0.015) and tumor grade (P=0.022). Furthermore, LINC00365 expression was significantly associated with lymph node metastasis (P=0.025). Gene set enrichment analysis revealed that LINC00501, LINC00365 and SOX21-AS1 were enriched in signaling pathways associated with GC. Reverse transcription-quantitative PCR analysis demonstrated that LINC00501 expression (P=0.043) was significantly upregulated in GC tissues, whereas the expression levels of LINC00365 (P=0.033) and SOX21-AS1 (P=0.037) were significantly downregulated in GC tissues. Taken together, the results of the present study suggest that LINC00501, LINC00365, SOX21-AS1, GK-IT1 and DLEU7-AS1 may be used as novel diagnostic biomarkers for GC, and may be functionally associated with GC development and progression.
| S-EPMC8063256 | biostudies-literature
Project description:Long non-coding RNAs (lncRNAs) can act as competing endogenous RNAs (ceRNAs), interacting with microRNAs (miRNAs) and playing an important role in tumor progression. However, the role of lncRNA-mediated ceRNAs in glioma remains largely unknown. The present study aimed to identify novel lncRNAs and their associated function in glioma. RNA sequencing and corresponding clinical data from patients with glioma were obtained from The Cancer Genome Atlas. A total of 598 glioma tissues and 5 normal brain tissues were analyzed in the present study. The differentially expressed (DE) lncRNAs, mRNAs and miRNAs were identified using R packages and were used to construct a ceRNA network. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed to investigate the biological functions of the DEmRNAs. Kaplan-Meier curve analysis was performed to investigate the association between DElncRNA expression and patient outcome. A total of 752 DElncRNAs, 2,079 DEmRNAs and 113 DEmiRNAs were identified between glioma and normal tissues. A lncRNA-miRNA-mRNA ceRNA network consisting of 61 lncRNAs, 12 miRNAs and 92 mRNAs was constructed. Survival analysis indicated that 36 DElncRNAs, 72 DEmRNAs and 3 DEmiRNAs were associated with overall survival in patients with glioma. The present study identified novel lncRNAs associated with survival prognosis and may facilitate further investigation of lncRNA-mediated ceRNA regulatory mechanisms in glioma.
| S-EPMC7436175 | biostudies-literature
Project description:BackgroundOsteosarcoma is the primary bone malignant neoplasm that often develops metastasis. Increasing evidences have shown that non-coding RNAs (ncRNAs) relate to the progression of osteosarcoma. However, the ncRNAs' roles in osteosarcoma metastasis are still unknown.MethodsDifferentially expressed (DE) RNAs were identified from Gene Expression Omnibus (GEO) database. Protein-protein interaction (PPI) of DE messenger RNAs (DEmRNAs) was built through STRING database. The target mRNAs and long ncRNAs (lncRNAs) of microRNAs (miRNA) were predicted through miRDB, Targetscan and Genecode databases, which then cross-checked with previously obtained DERNAs to construct competing endogenous RNA (ceRNA) network. All networks were visualized via Cytoscape and the hub RNAs were screened out through Cytoscape plug-in Cytohubba. The gene functional and pathway analyses were performed through DAVID and MirPath databases. The survival analyses of hub RNAs were obtained through Kaplan-Meier (KM) survival curves.ResultsFive hundred sixty-four DEmRNAs, 16 DElncRNAs and 22 DEmiRNAs were screened out. GO functional and KEGG pathway analyses showed that DERNAs were significantly associated with tumor metastasis. The ceRNA network including 6 lncRNAs, 55 mRNAs and 20 miRNAs were constructed and the top 10 hub RNAs were obtained. Above all, PI3K/AKT signaling pathway was identified as the most important osteosarcoma metastasis-associated pathway and its hub ceRNA module was constructed. The survival analyses showed that the RNAs in hub ceRNA module closely related to osteosarcoma patients' prognosis.ConclusionsThe current study provided a new perspective on osteosarcoma metastasis. More importantly, the RNAs in hub ceRNA module might act as the novel therapeutic targets and prognostic factors for osteosarcoma patients.
| S-EPMC7887822 | biostudies-literature
Project description:Emerging evidence indicates that long noncoding RNAs (lncRNAs) play important roles in the regulation of cell differentiation by acting as competing endogenous RNA (ceRNA). However, the regulatory mechanisms of lncRNA and the lncRNA-associated ceRNA network involved in adipogenic differentiation of chicken preadipocytes remain elusive. Here, we first constructed the chicken preadipocyte in vitro induction model. Then, we identified differentially expressed lncRNAs (DELs), miRNAs (DEMis), and mRNAs (DEMs) between differentiated and undifferentiated preadipocytes. Furthermore, we constructed the lncRNA associated ceRNA network by gene expression correlation analysis and target prediction of DELs, DEMis, and DEMs. Finally, we determined twelve candidate lncRNA-miRNA-mRNA interactions from the lncRNA associated ceRNA network. Eight out of the twelve interactions were validated by RT-qPCR, indicating their potential role in the regulation of chicken preadipocytes differentiation. Among the eight interactions, TCONS_00026544-gga-miR-128-1-5p-RASD1, TCONS_00055280-gga-miR-135a-5p-JAM3, TCONS_00055280-gga-miR-135a-5p-GPR133, TCONS_00055280-gga-miR-135a-5p-CLDN1, and TCONS_00055280-gga-miR-135a-5p-TMEM123 may promote adipogenic differentiation of chicken preadipocytes while TCONS_00057272-gga-miR-146a-3p-FOXO6, TCONS_00057242-gga-miR-6615-3p-FOXO6, and TCONS_00057242-gga-miR-6615-3p-ENSGALT00000043224 have the opposite effects. Our results not only provide novel insights into ceRNA roles of lncRNAs in chicken preadipocytes differentiation and but also contribute to a better understanding of chicken fat deposition.
| S-EPMC6826404 | biostudies-literature
Project description:Blood-tumor barrier (BTB) presents a major obstacle to brain drug delivery. Therefore, it is urgent to enhance BTB permeability for the treatment of glioma. In this study, we demonstrated that MIAT, ZAK, and phosphorylated NFκB-p65 (p-NFκB-p65) were upregulated, while miR-140-3p was downregulated in glioma-exposed endothelial cells (GECs) of BTB compared with those in endothelial cells cocultured with astrocytes (ECs) of blood-brain barrier (BBB). MIAT inhibited miR-140-3p expression, increased the expression of ZAK, enhanced the ratio of p-NFκB-p65:NFκB-p65, and promoted the endothelial leakage of BTB. Our current study revealed that miR-140-3p was complementary to the ZAK 3'untranslated regions (3'-UTR), and luciferase activity of ZAK was inhibited by miR-140-3p in 293T cells. MiR-140-3p silencing resulted in an increase in BTB permeability by targeting ZAK, while overexpression of miR-140-3p had the opposite results in GECs of BTB. Overexpression of ZAK induced an increase in BTB permeability, and this effect was related to ZAK's ability to mediate phosphorylation of NFκB-p65. Conversely, ZAK silencing get opposite results in GECs of BTB. As a molecular sponge of miR-140-3p, MIAT attenuated its negative regulation of the target gene ZAK by adsorbing miR-140-3p. P-NFκB-p65 as a transcription factor negatively regulated the expression of TJ-associated proteins by means of chip assay and luciferase assay. Single or combined application of MIAT and miR-140-3p effectively promoted antitumor drug doxorubicin (Dox) across BTB to induce apoptosis of glioma cells. In summary, MIAT functioned as a miR-140-3p sponge to regulate the expression of its target gene ZAK, which contribution to phosphorylation of NFκB-p65 was associated with an increase in BTB permeability by down-regulating the expression of TJ associated proteins, thereby promoting Dox delivery across BTB. These results might provide a novel strategy and target for chemotherapy of glioma.
| S-EPMC7603350 | biostudies-literature
Project description:Long non-coding RNAs (lncRNAs) have been indicated to serve critical roles in cancer development and progression. Long intergenic non-protein coding RNA 70 (LINC00707) was recently reported to be an oncogene involved in the tumorigenesis of several types of human cancer. However, the clinical role, biological functions and molecular mechanism of LINC00707 in colorectal cancer (CRC) remain unclear. The aim of the present study was to investigate the biological effects and mechanism of LINC00707 in CRC. Reverse transcription-quantitative PCR was used to detect the expression levels of LINC00707 in 65 CRC tissue samples and CRC cell lines (HCT116, HT29 and SW480). Cell Counting Kit-8 and colony formation assays were performed to investigate the effects of LINC00707 on CRC cell proliferation. A dual-luciferase reporter assay was conducted to investigate the mechanisms of LINC00707 in CRC. The upregulation of LINC00707 expression was significantly associated with tumor size, stage and poor survival in patients with CRC. LINC00707 also acted as an independent prognostic factor for CRC. Functional analyses revealed that the knockdown of LINC00707 could inhibit CRC cell proliferation. Furthermore, bioinformatics analysis demonstrated that microRNA (miR)-485-5p could directly bind to LINC00707, which was confirmed by a dual-luciferase reporter assay. In conclusion, the upregulation of LINC00707 is associated with a shorter survival time in patients with CRC. Knockdown of LINC00707 may inhibit the proliferation of CRC cells by binding with miR-485-5p.
| S-EPMC6966127 | biostudies-literature