Systematic analysis of key miRNAs and related signaling pathways in colorectal tumorigenesis

The development of colorectal cancers (CRC) is accompanied with the acquisition and maintenance of specific genomic alterations. These alterations can emerge in premalignant adenomas and faithfully maintained in highly advanced tumors. miRNAs are a class of small non-coding RNAs that are frequently deregulated in human cancers and negatively regulate a wide variety of protein coding genes. To identify the sequential alterations of miRNAs and its regulatory networks during CRC development and progression, we detected the miRNA expression profiles of tissue samples from normal colon, colorectal adenoma and CRC using miRNA microarray. qRT-PCR assay was used to validate and select the miRNAs with differential expression among the three groups, and the computer-aided algorithms of TargetScan, miRanda, miRwalk, RNAhybrid and PicTar were used to search for the possible targets of the selected 8 miRNAs (miR-18a, miR-18b, miR-31, miR-142-5p, miR-145, miR-212, miR-451, and miR-638) with continuous alterated expression. These potential target genes were enriched in several key signal transduction pathways (KEGG pathway analysis), which have been proved to be closely related to colorectal tumorigenesis. To confirm the reliability of the analyses, we identified that the metastasis-related gene ZO-1 is a certain target of miR-212 in CRC and keeps declining during CRC progression. By following these analyses, we might gain an in-depth understanding of the molecular regulatory networks of colorectal tumorigenesis and provide new potential targets for the diagnostic and therapeutic interventions of this disease. (C) 2015 Elsevier B.V. All rights reserved.