Dataset Information

Identification of miRNA/mRNA-Negative Regulation Pairs in Nasopharyngeal Carcinoma.

ABSTRACT: BACKGROUND Nasopharyngeal carcinoma (NPC) is a common malignancy in South-East Asia. NPC is characterized by distant metastasis and poor prognosis. The pathophysiological mechanism of nasopharyngeal carcinoma is unknown. This study aimed to identify the crucial miRNAs in nasopharyngeal carcinoma and their target genes, and to discover the potential mechanism of nasopharyngeal carcinoma development. MATERIAL AND METHODS Microarray expression profiling of miRNA and mRNA from the Gene Expression Omnibus database was downloaded, and we performed a significance analysis of differential expression. An interaction network of miRNAs and target genes was constructed. The underlying function of differentially expressed genes was predicted through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. To validate the microarray analysis data, significantly different expression levels of miRNAs and target genes were validated by quantitative real-time polymerase chain reaction. RESULTS We identified 27 differentially expressed miRNAs and 982 differentially expressed mRNAs between NPC and normal control tissues. 12 miRNAs and 547 mRNAs were up-regulated and 15 miRNAs and 435 mRNAs were down-regulated in NPC samples. We found a total of 1185 negative correlation pairs between miRNA and mRNA. Differentially expressed target genes were significantly enriched in pathways in cancer, cell cycle, and cytokine-cytokine receptor interaction signaling pathways. Significantly differentially expressed miRNAs and genes, such as hsa-miR-205, hsa-miR-18b, hsa-miR-632, hsa-miR-130a, hsa-miR-34b, PIGR, SMPD3, CD22, DTX4, and CDC6, may play essential roles in the development of nasopharyngeal carcinoma. CONCLUSIONS hsa-miR-205, hsa-miR-18b, hsa-miR-632, hsa-miR-130a, and hsa-miR-34b may be related to the development of nasopharyngeal carcinoma by regulating the genes involved in pathways in cancer and cell cycle signaling pathways.

SUBMITTER: Liu M

PROVIDER: S-EPMC4928598 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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Identification of miRNA/mRNA-Negative Regulation Pairs in Nasopharyngeal Carcinoma.

Liu Minglei M Zhu Kangru K Qian Xinmei X Li Wei W

Medical science monitor : international medical journal of experimental and clinical research 20160628

BACKGROUND Nasopharyngeal carcinoma (NPC) is a common malignancy in South-East Asia. NPC is characterized by distant metastasis and poor prognosis. The pathophysiological mechanism of nasopharyngeal carcinoma is unknown. This study aimed to identify the crucial miRNAs in nasopharyngeal carcinoma and their target genes, and to discover the potential mechanism of nasopharyngeal carcinoma development. MATERIAL AND METHODS Microarray expression profiling of miRNA and mRNA from the Gene Expression Om ...[more]

PMID: 27350400

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Project description:PurposeNasopharyngeal carcinoma (NPC) is one of the most common malignant tumors of the head and neck. This study aimed to investigate the crucial genes and regulatory networks involved in the carcinogenesis of NPC using a bioinformatics approach.MethodsFive mRNA and two miRNA expression datasets were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) and miRNAs (DEMs) between NPC and normal samples were analyzed using R software. The WebGestalt tool was used for functional enrichment analysis, and protein-protein interaction (PPI) network analysis of DEGs was performed using STRING database. Transcription factors (TFs) were predicted using TRRUST and Transcriptional Regulatory Element Database (TRED). Kinases were identified using X2Kgui. The miRNAs of DEGs were predicted using miRWalk database. A kinase-TF-mRNA-miRNA integrated network was constructed, and hub nodes were selected. The hub genes were validated using NPC datasets from the GEO and Oncomine databases. Finally, candidate small-molecule agents were predicted using CMap.ResultsA total of 122 DEGs and 44 DEMs were identified. DEGs were associated with the immune response, leukocyte activation, endoplasmic reticulum stress in GO analysis, and the NF-κB signaling pathway in KEGG analysis. Four significant modules were identified using PPI network analysis. Subsequently, 26 TFs, 73 kinases, and 2499 miRNAs were predicted. The predicted miRNAs were cross-referenced with DEMs, and seven overlapping miRNAs were selected. In the kinase-TF-mRNA-miRNA integrated network, eight genes (PTGS2, FN1, MMP1, PLAU, MMP3, CD19, BMP2, and PIGR) were identified as hub genes. Hub genes were validated with consistent results, indicating the reliability of our findings. Finally, six candidate small-molecule agents (phenoxybenzamine, luteolin, thioguanosine, reserpine, blebbistatin, and camptothecin) were predicted.ConclusionWe identified DEGs and an NPC regulatory network involving kinases, TFs, mRNAs, and miRNAs, which might provide promising insight into the pathogenesis, treatment, and prognosis of NPC.

Project description:PurposeMicroRNA (miRNA) function via base-pairing with complementary sequences within mRNA molecules. This study aims to identify critical miRNA-mRNA regulation pairs contributing to lung adenocarcinoma (LUAD) pathogenesis.Patients and methodsMiRNA and mRNA microarray and RNA-sequencing datasets were downloaded from gene expression omnibus (GEO) and the cancer genome atlas (TCGA) databases. Differential miRNAs (DE-miRNAs) and mRNAs (DE-mRNAs) were screened by the GEO2R tool and R packages. DAVID, DIANA, and Hiplot tools were used to perform gene enrichment analysis. The pairs of miRNA-mRNA were screened from the experimentally validated miRNA-target interactions databases (miRTarBase and TarBase). External validation was carried out in 30 pairs of LUAD tissues by quantitative reverse transcription and polymerase chain reaction (qRT-PCR). The diagnostic value of the miRNA-mRNA regulation pairs was evaluated by receiver operating characteristic curve (ROC) and decision curve analysis (DCA). Biological function assay was were also performed to confirm the function of miRNA-mRNA axis in LUAD progression. The study also performed the clinical, survival and tumor-associated phenotypic analysis of miRNA-mRNA pairs.ResultsA total of 7 miRNA and 13 mRNA expression datasets from GEO were analyzed, and 11 DE-miRNAs (5 down-regulated and 6 up-regulated in LUAD tissues) and 128 DE-mRNAs (30 up-regulated and 98 down-regulated in LUAD tissues) were identified. The pairs of miR-1-3p(down) and CENPF(up) and miR-126-5p(down) and UGT8(up) were verified in the external validation cohort (30 LUAD vs. 30 NC) using qRT-PCR. Areas under the ROC curve of the two miRNA-mRNA regulation pairs panel were 0.973 in TCGA-LUAD and 0.771 in the external validation. The DCA also showed that the miRNA-mRNA regulation pairs had an excellent diagnostic performance distinguishing LUAD from normal controls. The expression of the regulation pairs is different in different ages, TNM stages, and gender. The overexpression of miR-1-3p and miR-126-5p significantly inhibited the proliferation and migration of LUAD cells. Correlation analysis showed that CENPF correlated with prognosis and tumor immunity.ConclusionsThe research identified potential miRNA-mRNA regulation pairs, providing a new idea for exploring the genesis and development of LUAD.

Project description:Nowadays, the current bioinformatic methods have been increasingly applied in the field of oncological research. In this study, we expect a better understanding of the molecular mechanism of gastric cancer from the bioinformatic methods. By systematically addressing the differential expression of microRNAs (miRNAs) and mRNAs between gastric cancer specimens and normal gastric specimens with the application of bioinformatics tools, A total of 206 DEGs and 38 DEMs were identified. The Gene Ontology (GO) analysis of Annotation, Visualization and Integrated Discovery (DAVID) database revealed that the differentially expressed genes (DEGs) were significantly enriched in biological process, molecular function and cellular component, while Kyoto Encyclopedia of Genes and Genomes (KEGG) database showed DEGs were significantly enriched in 8 signal pathways. The miRNA-gene regulatory network was constructed based on 385 miRNA-gene (DEM-DEG) pairs, consisting of 35 miRNAs and 107 target genes. In the regulatory network, the top 5 up-regulated genes were Transmembrane Protease, Serine 11B (TMPRSS11B), regulator of G protein signaling 1 (RGS1), cysteine rich angiogenic inducer 61 (CYR61), inhibin subunit beta A (INHBA), syntrophin gamma 1 (SNTG1), and the top 5 down-regulated genes were tumor necrosis factor receptor superfamily, member 19 (TNFRSF19), pleckstrin homology domain containing B2 (PLEKHB2), Tax1 binding protein 3 (TAX1BP3), presenilin enhancer, gamma-secretase subunit (PSENEN), NME/NM23 nucleoside diphosphate kinase 3 (NME3). Based on the gastric cancer patient database from Kaplan-Meier Plotter tools, we found that 8 of 10 genes with most significant changes in the miRNA-gene regulatory network possessed a prognostic value for survival time of gastric cancer patients. Patients with higher level of RGS1, PLEKHB2, TAX1BP3 and PSENEN in gastric cancer had a longer survival time compared with the patients with lower level of these genes. On the contrary, patients with higher level of INHBA, SNTG1, TNFRSF19 and NME3 were found associated with a shorter survival time. In conclusion, our findings provided several potential targets regarding gastric cancer, which may result in a new strategy to treat gastric cancer from a system rather than a single-gene perspective.

Project description:BackgroundNasopharyngeal cancer (NPC) has a high incidence in Southern China and Asia, and its survival is extremely poor in advanced patients. MiRNAs play critical roles in regulating gene expression and serve as therapeutic targets in cancer. This study sought to disclose key miRNAs and target genes responsible for NPC prognosis and endocrine metabolism.Materials and methodsThree datasets (GSE32960, GSE70970, and GSE102349) of NPC samples came from Gene Expression Omnibus (GEO). Limma and WGCNA were applied to identify key prognostic miRNAs. There were 12 types of miRNA tools implemented to study potential target genes (mRNAs) of miRNAs. Univariate Cox regression and stepAIC were introduced to construct risk models. Pearson analysis was conducted to analyze the correlation between endocrine metabolism and RiskScore. Single-sample gene set enrichment analysis (ssGSEA), MCP-counter, and ESTIMATE were performed for immune analysis. The response to immunotherapy was predicted by TIDE and SubMap analyses.ResultsTwo key miRNAs (miR-142-3p and miR-93) were closely involved in NPC prognosis. The expression of the two miRNAs was dysregulated in NPC cell lines. A total of 125 potential target genes of the key miRNAs were screened, and they were enriched in autophagy and mitophagy pathways. Five target genes (E2F1, KCNJ8, SUCO, HECTD1, and KIF23) were identified to construct a prognostic model, which was used to divide patients into high group and low group. RiskScore was negatively correlated with most endocrine-related genes and pathways. The low-risk group manifested higher immune infiltration, anticancer response, more activated immune-related pathways, and higher response to immunotherapy than the high-risk group.ConclusionsThis study revealed two key miRNAs that were highly contributable to NPC prognosis. We delineated the specific links between key miRNAs and prognostic mRNAs with miRNA-mRNA networks. The effectiveness of the five-gene model in predicting NPC prognosis as well as endocrine metabolism provided a guidance for personalized immunotherapy in NPC patients.

Dataset Information

Identification of miRNA/mRNA-Negative Regulation Pairs in Nasopharyngeal Carcinoma.

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Identification of miRNA/mRNA-Negative Regulation Pairs in Nasopharyngeal Carcinoma.

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