Abstract

MiRNAs are small noncoding RNA molecules that are often aberrantly over- or underexpressed in tumors, including colorectal cancer (CRC). Due to their capacity to regulate and thus fine-tune the expression of multiple target genes relevant in tumorigenesis, tumor progression, angiogenesis, metastasis and sensitivity towards chemotherapy, they influence various pivotal cellular processes with prognostic and therapeutic relevance in CRC.

This review provides a comprehensive overview of miRNAs with established functional relevance in colorectal cancer, their established target genes and the resulting cellular and pathological phenotype(s). Furthermore, approaches towards therapeutic miRNA-based intervention are discussed. Those include viral or non-viral approaches of miRNA replacement therapy in the case of tumor-suppressing miRNAs, and multiple strategies for the inhibition of oncogenic miRNAs. Beyond the analysis of the functional relevance of a given miRNA as target molecule or a miRNA-based drug, several studies in preclinical in vivo models are described that provide the basis for possible future therapeutic intervention in man.

Keywords: MiRNAs, colorectal cancer, anticancer therapy, novel miRNA-based therapies, miRNA replacement, antimiRs, nanoparticles, RNA delivery, phenotype, target molecule