Abstract

Background and AimAltered expression of microRNAs (miRNAs) hallmarks many cancer types. The study of the associations of miRNA expression profile and cancer phenotype could help identify the links between deregulation of miRNA expression and oncogenic pathways.MethodsExpression profiling of 866 human miRNAs in 19 colorectal and 17 pancreatic cancers and in matched adjacent normal tissues was investigated. Classical paired t-test and random forest analyses were applied to identify miRNAs associated with tissue-specific tumors. Network analysis based on a computational approach to mine associations between cancer types and miRNAs was performed.ResultsThe merge between the two statistical methods used to intersect the miRNAs differentially expressed in colon and pancreatic cancers allowed the identification of cancer-specific miRNA alterations. By miRNA-network analysis, tissue-specific patterns of miRNA deregulation were traced: the driving miRNAs were miR-195, miR-1280, miR-140-3p and miR-1246 in colorectal tumors, and miR-103, miR-23a and miR-15b in pancreatic cancers.ConclusionMiRNA expression profiles may identify cancer-specific signatures and potentially useful biomarkers for the diagnosis of tissue specific cancers. miRNA-network analysis help identify altered miRNA regulatory networks that could play a role in tumor pathogenesis.

Highlights

  • MicroRNAs are small non-protein coding RNA molecules that regulate gene expression mainly at the level of protein synthesis [1]

  • Aberrant expression of miRNAs can arise from deletion, mutation, and methylation of miRNA-encoding genes, many of which located at genomic fragile sites or regions frequently deleted or amplified in cancer [3]

  • We investigated expression patterns of miRNAs in colorectal (CRC) and pancreatic cancer (PC) with the intent to identify miRNA regulatory networks likely involved in oncogenic pathways by evaluating cancer-specific signatures through the analysis of the relationship between miRNA expression profile and cancer lineages

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Summary

Introduction

MicroRNAs (miRNAs) are small non-protein coding RNA molecules that regulate gene expression mainly at the level of protein synthesis [1]. They represent an evolutionary highly conserved system that controls crucial cellular processes, such as development, differentiation, proliferation, apoptosis, and metabolism [2]. Aberrant expression of miRNAs can arise from deletion, mutation, and methylation of miRNA-encoding genes, many of which located at genomic fragile sites or regions frequently deleted or amplified in cancer [3] Based on these premises, they have been proven to interact with potential oncogenes or tumor suppressors [4]. The study of the associations of miRNA expression profile and cancer phenotype could help identify the links between deregulation of miRNA expression and oncogenic pathways

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