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BACKGROUND Medullary thyroid carcinoma (MTC), a rare type of thyroid cancer, is a big challenge in clinical treatment. However, the pathogenesis of MTC remains poorly understand. MicroRNAs (miRNAs) were previously demonstrated to be involved in the pathogenesis of MTC, however, the roles of majority of miRNAs in MTC are still undetermined. MATERIAL AND METHODS Two GEO miRNA expression profiles (GSE40807, GSE97070) were downloaded, and the differentially expressed miRNAs (DEmiRNAs) of GSE40807 and GSE97070 were analyzed by bioinformatics methods. Expressions of miRNAs were detected by quantitative real-time polymerase chain reaction; cell proliferation was examined through Cell Counting Kit-8, colony formation and in vivo tumor growth assays; the interaction between miRNA and mRNA was verified by dual-luciferase reporter assay; functional analysis of target genes was performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID, www.david.ncifcrf.gov) software. RESULTS Ten miRNAs were identified to be dysregulated in both GSE40807 and GSE97070 datasets, and miR-31-3p showed the highest change fold (Log fold change=-3.460625 in GSE40807 and Log fold change=-0.07084374 in GSE97070). MiR-31-3p expression was significantly downregulated in MTC, and low miR-31-3p expression showed a poor prognosis relative to high miR-31-3p expression (P<0.05). Functionally, miR-31-3p inhibited MTC cell proliferation in vitro and in vivo. Functional analysis also showed that the target genes of miR-31-3p were involved in numerous of biochemical processes and pathways, of which Ras signaling pathway was selected for further study. RASA2, overexpressed in MTC, were negatively regulated by miR-31-3p. In addition, we found that knockdown of RASA2 inhibited MTC cell proliferation. CONCLUSIONS Reduced expression level of miR-31-3p might play a key role in the tumorigenesis of MTC by targeting critical pathways, especially Ras signaling pathway.
Pubmed ID: 31298226
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View all literature mentionsBioinformatics resource system including web server and web service for functional annotation and enrichment analyses of gene lists. Consists of comprehensive knowledgebase and set of functional analysis tools. Includes gene centered database integrating heterogeneous gene annotation resources to facilitate high throughput gene functional analysis.
View all literature mentionsSoftware package used for interactive, or batched, statistical analysis in social science, health sciences and marketing. Software platform offers advanced statistical analysis, a library of machine-learning algorithms, text analysis, open-source extensibility, integration with big data and deployment into applications.Versions that were produced by SPSS Inc. before the IBM acquisition (Versions 18 and earlier) would be given origin or publisher of SPSS Inc. in Chicago.
View all literature mentionsTHIS RESOURCE IS NO LONGER IN SERVICE, documented on January 19, 2022.
View all literature mentionsIntegrated database resource consisting of 16 main databases, broadly categorized into systems information, genomic information, and chemical information. In particular, gene catalogs in completely sequenced genomes are linked to higher-level systemic functions of cell, organism, and ecosystem. Analysis tools are also available. KEGG may be used as reference knowledge base for biological interpretation of large-scale datasets generated by sequencing and other high-throughput experimental technologies.
View all literature mentionsSoftware tool for versatile matrix visualization and analysis. Program to generate heatmaps from input data. JavaScript matrix visualization and analysis.
View all literature mentionsMus musculus with name Crl:NU(NCr)-Foxn1nu from IMSR.
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