MicroRNA and targeted mRNA expression profiling analysis in human colorectal adenomas and adenocarcinomas

Abstract

Background: Colorectal cancer (CRC) mainly develops from colorectal adenomas (CRAs). MicroRNAs (miRs) are short non-coding transcripts that regulate gene expression by binding to target mRNAs, preventing their expression. It was suggested that miRs were involved in cancer as tumour suppressors or oncogenes, thereby being also potential cancer biomarkers. We conducted an expression analysis of miRNAs and several of their target mRNAs, by using microarrays and quantitative Reverse Transcription-Polymerase Chain Reaction (RT-PCR) (RT-qPCR), in CRA and CRC, as compared to normal mucosa (NOR), in order to identify candidate miRNAs involved in CRC progression.

Results: Microarray, together with confirmatory RT-qPCR analyses, showed 17 significantly deregulated miRNAs in colorectal lesions. While, as expected, some miRNAs have been previously reported to be associated with CRC, including miR-21 and miR-145, others were new (miR-125a-5p and miR-320 family). Some miRNAs were specific for the CRC versus NOR comparison (miR-320b), or for the CRA versus NOR comparison (miR-15b or miR-16), but several of them (miR-21, miR-24, miR-145, mir-150, miR-378) were deregulated in both CRAs and CRCs, as compared to NOR. The impact of these changes in miR expression on target genes is suggested by the associated deregulation of these genes in CRA and CRC.

Conclusions: We confirmed that several miRNAs were abnormally expressed in colorectal lesions, identified new deregulated miRs, and showed that several miRNAs could mark the transition from NOR to CRA, thereby marking progression from the early steps of cancer.

Keywords: Biomarker; Colorectal adenoma; Colorectal cancer; miRNA.