ABSTRACT: Purpose: MicroRNAs play a prominent role in a variety of physiological and pathological biological processes, including cancer. For rectal cancers, only limited data are available on microRNA expression profiles, while the underlying genomic and transcriptomic aberrations have been firmly established. We therefore aimed to comprehensively map the microRNA expression patterns of this disease. Experimental design: Tumor biopsies and corresponding matched mucosa samples were prospectively collected from 72 patients (68 tumors and 70 normal mucosa) with locally advanced rectal cancers. Total RNA was extracted, and tumor and mucosa microRNA expression profiles were subsequently established for all patients. The expression of selected microRNAs was validated using semi-quantitative real-time PCR. Results: Forty-nine microRNAs were significantly differentially expressed (log2-fold difference >0.5 and P<0.001) between rectal cancer and normal rectal mucosa. The predicted targets for the identified microRNAs were enriched for the following KEGG pathways: Wnt, TGF-beta, mTOR, insulin, MAPK, and ErbB signaling. Between rectal tumor and normal tissue, miR-492, miR-542-5p, miR-584, miR-483-5p, miR-144, miR-2110, miR-652*, miR-375, miR-147b, miR-148a, miR-190, miR-26a/b, and miR-338-3p were found to be differentially expressed. Of clinical impact, miR-135b expression correlated significantly with overall survival that could be validated in a larger multicenter patient set (n=94). Conclusion: The comprehensive analysis of the rectal cancer microRNAome uncovered novel microRNAs and pathways associated with rectal cancer. This information contributes to a detailed view of rectal cancer. The identification and validation of miR-135b will help to identify novel molecular targets and pathways for therapeutic exploitation.
