Dataset Information

Integrated miRNA profiling and bioinformatics analyses reveal upregulated miRNAs in gastric cancer.

ABSTRACT: Gastric cancer is one of the most common malignancies in China and exhibits a poor prognosis. The most significant challenge for gastric cancer treatment is the absence of early diagnostic biomarkers. MicroRNAs (miRNAs) are small non-coding RNAs, which possess clinical value in a number of different types of cancer. The current study identified 13 miRNAs (hsa-miR-22, hsa-miR-545, hsa-let-7i, hsa-miR-15b, hsa-miR-221, hsa-miR-196a, hsa-miR-20a, hsa-miR-196b, hsa-miR-93, hsa-miR-19a, hsa-miR-503, hsa-miR-106b and hsa-miR-18a) that were significantly overexpressed in GC, by analyzing 1,000 GC samples included in four public datasets, including GSE23739, GSE78091, GSE30070 and The Cancer Genome Atlas. Furthermore, it was revealed that the expression levels of these 13 miRNAs were significantly higher in gastric cancer tissues of grades I, II and III compared with normal controls. Gene ontology analysis and Kyoto Encyclopedia of Genes and Genomes analysis demonstrated that the differentially expressed miRNAs were involved in regulating transcription, protein amino acid phosphorylation, signal transduction, protein binding, zinc ion binding, the mitogen-activated protein kinase signaling pathway and focal adhesion. In summary, the present study may provide potential new therapeutic and prognostic targets for gastric cancer.

SUBMITTER: Yuan C

PROVIDER: S-EPMC6607103 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Integrated miRNA profiling and bioinformatics analyses reveal upregulated miRNAs in gastric cancer.

Yuan Chen C Zhang Yue Y Tu Wenwen W Guo Yusheng Y

Oncology letters 20190619 2

Gastric cancer is one of the most common malignancies in China and exhibits a poor prognosis. The most significant challenge for gastric cancer treatment is the absence of early diagnostic biomarkers. MicroRNAs (miRNAs) are small non-coding RNAs, which possess clinical value in a number of different types of cancer. The current study identified 13 miRNAs (hsa-miR-22, hsa-miR-545, hsa-let-7i, hsa-miR-15b, hsa-miR-221, hsa-miR-196a, hsa-miR-20a, hsa-miR-196b, hsa-miR-93, hsa-miR-19a, hsa-miR-503, ...[more]

PMID: 31423268

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Project description:Background and Objectives: To screen key miRNAs and their target genes related to Toll-like receptor (TLR) activation in gastric cancer (GC) cells and analyze them bioinformatically. Materials and Methods: Venn diagrams were obtained to screen miRNAs that were upregulated/downregulated in both GSE54129 and GSE164174. The miRTarBase database was used to predict the target genes of upregulated miRNAs. The differentially expressed genes in the regulatory network were analyzed. miR-16-5p expression in different tissue samples and the variations in the methylation states of four hub genes were measured. Results: We found that GSE54129 included 21 normal gastric tissues and 111 gastric cancer tissues, GSE164174 included 1417 normal gastric tissues and 1423 gastric cancer tissues. Venn diagram analysis results showed that compared with the control group, a total of 68 DEmiRNAs were upregulated in the GSE54129 and GSE164174 datasets, and no common downregulated DEmiRNAs were found. On further analysis of the GSE108345 dataset, we obtained the competing endogenous RNA (ceRNA) network associated with the activation of TLRs, and listed the top 10 lncRNA-miRNA-mRNA networks, including 10 miRNAs, 86 mRNA and 134 lncRNAs. Cytological HuBBA scores yielded a total of 1 miRNA, 16 mRNAs and 45 lncRNAs, of which miR-16-5p scored the highest as it was considered a key miRNA for TLR activation in GC cells, which are important in response against microorganisms. The results of Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that endocytosis, microRNAs in cancer and the PI3K-Akt signaling pathway are related to TLR signaling. The results of in vivo experiments indicated that miR-16-5p was highly expressed in gastric cancer cells and tissues. Conclusions: Hsa-miR-16-5p's target genes mainly play a role by regulating the expression of four genes-MCL1, AP2B1, LAMB1, and RAB11FIP2. The findings provide a scientific basis for the development of immunotherapy for GC.

Project description:BackgroundOsteoarthritis (OA) is a chronic degenerative joint disease and the most frequent type of arthritis. This study aimed to identify the key miRNAs and genes associated with OA progression.MethodsThe GSE105027 (microRNA [miRNA/miR] expression profile; 12 OA samples and 12 normal samples) and GSE48556 (messenger RNA [mRNA] expression profile; 106 OA samples and 33 normal samples) datasets were selected from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) and miRNAs (DEMs) were analyzed using the limma and ROCR packages in R, respectively. The target genes that negatively correlated with the DEMs were predicted, followed by functional enrichment analysis and construction of the miRNA-gene and miRNA-transcription factor (TF)-gene regulatory networks. Additionally, key miRNAs and genes were screened, and their expression levels were verified by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR).ResultsA total of 1696 DEGs (739 upregulated and 957 downregulated) and 108 DEMs (56 upregulated and 52 downregulated) were identified in the OA samples. Furthermore, 56 target genes that negatively correlated with the DEMs were predicted and found to be enriched in three functional terms (e.g., positive regulation of intracellular protein transport) and three pathways (e.g., human cytomegalovirus infection). In addition, three key miRNAs (miR-98-5p, miR-7-5p, and miR-182-5p) and six key genes (murine double minute 2, MDM2; glycogen synthase kinase 3-beta, GSK3B; transmembrane P24-trafficking protein 10, TMED10; DDB1 and CUL4-associated factor 12, DCAF12; caspase 3, CASP3; and ring finger protein 44, RNF44) were screened, among which the miR-7-5p → TMED10/DCAF12, miR-98-5p → CASP3/RNF44, and miR-182-5p → GSK3B pairs were observed in the regulatory network. Moreover, the expression levels of TMED10, miR-7-5p, CASP3, miR-98-5p, GSK3B, and miR-182-5p showed a negative correlation with qRT-PCR verification.ConclusionMiR-98-5p, miR-7-5p, miR-182-5p, MDM2, GSK3B, TMED10, DCAF12, CASP3, and RNF44 may play critical roles in OA progression.

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Integrated miRNA profiling and bioinformatics analyses reveal upregulated miRNAs in gastric cancer.

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Integrated miRNA profiling and bioinformatics analyses reveal upregulated miRNAs in gastric cancer.

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