Abstract
ABSTRACTMicroRNAs (miRNAs) are small single-stranded RNAs that repress mRNA translation and trigger mRNA degradation. Of the ∼1900 miRNA-encoding genes present in the human genome, ∼250 miRNAs are reported to have changes in abundance or altered functions in colorectal cancer. Thousands of studies have documented aberrant miRNA levels in colorectal cancer, with some miRNAs reported to actively regulate tumorigenesis. A recurrent phenomenon with miRNAs is their frequent participation in feedback loops, which probably serve to reinforce or magnify biological outcomes to manifest a particular cellular phenotype. Here, we review the roles of oncogenic miRNAs (oncomiRs), tumor suppressive miRNAs (anti-oncomiRs) and miRNA regulators in colorectal cancer. Given their stability in patient-derived samples and ease of detection with standard and novel techniques, we also discuss the potential use of miRNAs as biomarkers in the diagnosis of colorectal cancer and as prognostic indicators of this disease. MiRNAs also represent attractive candidates for targeted therapies because their function can be manipulated through the use of synthetic antagonists and miRNA mimics.
Highlights
Colorectal cancer (CRC) is the fourth leading cause of cancerrelated deaths worldwide (McGuire, 2016) and the second leading cause of cancer-related deaths in the USA
Aside from acting as an effector of TP53, miR-34a expression downstream of the canonical oncogenic transcription factors, MYC and STAT3, described above, provides negative feedback on tumor cell proliferation, survival and metastasis, which highlights the multifaceted mechanisms by which miR-34 represses tumorigenesis
In the breast cancer cell line MCF10A, miR-21 activation appears to be necessary for the optimal activation of NFΚB, which leads to a positive feedback loop that activates the expression of IL6 and STAT3, which directly activates the transcription of miR-21 (Iliopoulos et al, 2010)
Summary
Colorectal cancer (CRC) is the fourth leading cause of cancerrelated deaths worldwide (McGuire, 2016) and the second leading cause of cancer-related deaths in the USA (https://www.cdc.gov/ cancer/colorectal/). Human DICER1 appears to have a tumor-suppressive role in CRC cell lines (Iliou et al, 2014), and in other cancers, suggesting that miRNA biogenesis is essential for repressing tumorigenesis.
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