Bioinformatics Analysis of The most Potent Tumor Suppressor MicroRNAs in Hepatocellular carcinoma Revealing  New Links to Immune System Modulation And Insights into Cancer Pathways — ASN Events
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  3. Bioinformatics Analysis of The most Potent Tumor Suppressor MicroRNAs in Hepatocellular carcinoma Revealing  New Links to Immune System Modulation And Insights into Cancer Pathways

Bioinformatics Analysis of The most Potent Tumor Suppressor MicroRNAs in Hepatocellular carcinoma Revealing  New Links to Immune System Modulation And Insights into Cancer Pathways (#89)

Mahmoud ElHefnawi 1 , Bangly Soliman 1 2 , Mohamed Ghazy 3 , Ahmed Salem 3
  1. Centre of Excellence for Advanced Sciences, Informatics and Systems , National Research Centre, Cairo, Egypt
  2. Biochemisty, Faculty of Science Ainshams University, Cairo, Egypt
  3. Biochemisty, Faculty of Science Ainshams University, Cairo, Egypt

Interest in miR-34a, let-7a, and miR-199 a&b is sparking as more insights into their roles as master regulators of cellular processes emerge. These 3 micro-RNAs possess tumor suppressor activity that makes them potential new anti-cancer agents for hepatocellular carcinoma. In our current study, we performed in silico functional enrichment analysis using four innovative servers (miRror Suite, miRWalk, miRGator v3.0, and GeneTrail) in order to demonstrate the combinatorial and individual regulation of these 3 suppressor miRs on the expression of hundreds specific target genes involved in a variety of pathways of immune system and HCC/cancer hallmarks. We determined eighty seven common target genes which are coordinately regulated by our 3 miRNA set using miRror 2.0 target prediction programs with p-value< or = 0.05 and miRror Internal Score (miRIS) = 0. Furthermore, functional enrichment analysis of these miRNA targets by DAVID functional annotation (KEGG, BIOCARTA, GO) and REACTOME reveals two pathways linked to immune system.  Eight pathways linked to HCC/cancer hallmarks and two pathways mediate interconnected dual function between immune system and HCC/cancer hallmarks. Moreover, there are seven functionally enriched GO terms. An additional interesting findings from miRror suite is illustrating the protein-protein interactions network for the predicted common target genes of our 3 miRNA set by STRING cytoscape.Regarding the individual analysis for each miRNA of interest through miRWalk database we could determine some of the novel oncogenes which are regulated by these miRs. Furthermore, by mirwalk pathway analysis we determined many enriched immune system pathways and other cancer hallmarks pathways where these 3 miRs mediate regulation. On using miRGator v3.0 server, we analyzed deep sequencing data of liver hepatocellular carcinoma (TCGA-LIHC) under our own approaches to determine some putative targets with significant anti-correlation of expression with the canonical mature miR-34a,let-7a, miR-199 a&b , based on Pearson and Spearman correlations.As result, The number of target genes for miR-34a were 36, for let-7a were 34, for miR-199a were 29 and for miR-199b were 26. Then, GeneTrail Server was used for functional enrichment analysis.