Integrative Analysis of Transcriptome and MicroRNome Profiles inCholangiocarcinoma
2017
Aim: To identify deregulated expression of miRNAs and target genes in cholangiocarcinoma (CCA), as well as
drug-gene interactions that may be useful for patient treatment.
Methods: We analyzed quantitative transcriptome and miRNA deep sequencing expression data from 45
samples, 36 CCA and 9 histologically normal biliary tissues, obtained from the public repository The Cancer
Genome Atlas (TCGA). Bioinformatic methods were used to identify and integrate differential expression of miRNA
and transcriptome profiles in CCA vs. normal tissues. Deregulated miRNA and corresponding target genes were
identified and mapped into miRNA-mRNA networks.
Results: Results showed 64 differentially expressed miRNAs (48 over and 16 under-expressed) between
CCA and corresponding normal biliary tissues. Additionally, 432 genes (180 over and 252 under-expressed) were
identified between CCA and normal samples. We identified individual miRNAs with the largest number of gene
targets. Among these, miR-125a was over-expressed and had the highest number of direct interactions with 33
mRNA targets. miRNAs miR-122 and miR-139 were the under-expressed miRNAs with the highest number of
interactions (9 targets each). miR-122 was found to modulate the expression of the transcription factor FOXM1,
known to be involved in tumorigenesis and the matrix metalloproteinase MMP7, an important mediator of tumor
invasion. miR-148 and miR-194 were predicted to modulate NQO1, which is up-regulated in cancer and associated
with treatment resistance in cholangiocarcinoma.
Conclusion: The novelty of our study is the identification of complex deregulated networks of miRNAs and
target genes in CCA. miRNAs with a large number of targets may have a higher functional impact on cell regulation.
These findings contribute for a better understanding of CCA biology. Identified miRNAs and target genes are
potential candidates for the design of validation strategies towards the characterization of clinically applicable
biomarkers; such biomarkers may be useful for the development of molecularly-targeted therapeutics that can
benefit patients.
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