Integrative Analysis of Transcriptome and MicroRNome Profiles in Cholangiocarcinoma

Aim: To identify deregulated expression miRNAs target genes in cholangiocarcinoma (CCA), as well asdrug-gene interactions that may be useful for patient treatment.Methods: We analyzed quantitative transcriptome deep sequencing expression data from 45 samples, 36 CCA 9 histologically normal biliary tissues, obtained from the public repository The Cancer Genome Atlas (TCGA). Bioinformatic methods used to identify integrate differential expression miRNA transcriptome profiles in CCA vs. normal tissues. Deregulated corresponding target genes wereidentified mapped into miRNA-mRNA networks.Results: Results showed 64 differentially expressed miRNAs (48 over 16 under-expressed) CCA corresponding normal biliary tissues. Additionally, 432 genes (180 over 252 under-expressed) were identified between CCA normal samples. We identified individual miRNAs with the largest number gene targets. Among these, miR-125a was over-expressed had the highest number direct interactions with 33 mRNA targets. miRNAs miR-122 miR-139 the under-expressed miRNAs with the highest number of interactions (9 targets each). miR-122 was found to modulate the expression the transcription factor FOXM1, known to be involved in tumorigenesis the matrix metalloproteinase MMP7, an important mediator tumor invasion. miR-148 miR-194 predicted to modulate NQO1, which is up-regulated in cancer associatedwith treatment resistance in cholangiocarcinoma.Conclusion: The novelty our study is the identification complex deregulated networks miRNAs and target genes in CCA. miRNAs with a large number targets may have a higher functional impact on cell regulation. These findings contribute for a better understanding CCA biology. Identified miRNAs target genes are potential candidates for the design validation strategies towards the characterization clinically applicable biomarkers; such biomarkers may be useful for the development molecularly-targeted therapeutics that canbenefit patients.