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miRFA: an automated pipeline for microRNA functional analysis with correlation support from TCGA and TCPA expression data in pancreatic cancer
Department of Surgical and Perioperative Sciences, Umeå University, Umeå, Sweden.
University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. Department of Physics, Chemistry and Biology, Bioinformatics, Linköping University, Linköping, Sweden. (Translationell bioinformatik, Translational bioinformatics)ORCID iD: 0000-0001-7804-1177
University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. (Translationell bioinformatik, Translational bioinformatics)ORCID iD: 0000-0001-6427-0315
Department of Surgical and Perioperative Sciences, Umeå University, Umeå, Sweden.
2019 (English)In: BMC Bioinformatics, ISSN 1471-2105, E-ISSN 1471-2105, Vol. 20, no 1, p. 1-17, article id 393Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: MicroRNAs (miRNAs) are small RNAs that regulate gene expression at a post-transcriptional level and are emerging as potentially important biomarkers for various disease states, including pancreatic cancer. In silico-based functional analysis of miRNAs usually consists of miRNA target prediction and functional enrichment analysis of miRNA targets. Since miRNA target prediction methods generate a large number of false positive target genes, further validation to narrow down interesting candidate miRNA targets is needed. One commonly used method correlates miRNA and mRNA expression to assess the regulatory effect of a particular miRNA. The aim of this study was to build a bioinformatics pipeline in R for miRNA functional analysis including correlation analyses between miRNA expression levels and its targets on mRNA and protein expression levels available from the cancer genome atlas (TCGA) and the cancer proteome atlas (TCPA). TCGA-derived expression data of specific mature miRNA isoforms from pancreatic cancer tissue was used.

RESULTS: Fifteen circulating miRNAs with significantly altered expression levels detected in pancreatic cancer patients were queried separately in the pipeline. The pipeline generated predicted miRNA target genes, enriched gene ontology (GO) terms and Kyoto encyclopedia of genes and genomes (KEGG) pathways. Predicted miRNA targets were evaluated by correlation analyses between each miRNA and its predicted targets. MiRNA functional analysis in combination with Kaplan-Meier survival analysis suggest that hsa-miR-885-5p could act as a tumor suppressor and should be validated as a potential prognostic biomarker in pancreatic cancer.

CONCLUSIONS: Our miRNA functional analysis (miRFA) pipeline can serve as a valuable tool in biomarker discovery involving mature miRNAs associated with pancreatic cancer and could be developed to cover additional cancer types. Results for all mature miRNAs in TCGA pancreatic adenocarcinoma dataset can be studied and downloaded through a shiny web application at https://emmbor.shinyapps.io/mirfa/ .

Place, publisher, year, edition, pages
BioMed Central, 2019. Vol. 20, no 1, p. 1-17, article id 393
Keywords [en]
Functional enrichment, Mature miRNA, Pancreatic cancer, TCGA, TCPA, miRNA functional analysis, miRNA target prediction
National Category
Bioinformatics and Systems Biology
Research subject
Bioinformatics; INF502 Biomarkers
Identifiers
URN: urn:nbn:se:his:diva-17456DOI: 10.1186/s12859-019-2974-3ISI: 000475761100001PubMedID: 31311505Scopus ID: 2-s2.0-85069159500OAI: oai:DiVA.org:his-17456DiVA, id: diva2:1338034
Available from: 2019-07-19 Created: 2019-07-19 Last updated: 2019-08-07Bibliographically approved

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