Abstract
Cancer is a complex disease involving alterations of multiple processes, with both genetic and epigenetic features contributing as core factors to the disease. In recent years, it has become evident that non-coding RNAs (ncRNAs), an epigenetic factor, play a key role in the initiation and progression of cancer. MicroRNAs, the most studied non-coding RNAs subtype, are key controllers in a myriad of cellular processes, including proliferation, differentiation, and apoptosis. Furthermore, the expression of miRNAs is controlled, concomitantly, by other epigenetic factors, such as DNA methylation and histone modifications, resulting in aberrant patterns of expression upon the occurrence of cancer. In this sense, aberrant miRNA landscape evaluation has emerged as a promising strategy for cancer management. In this review, we have focused on the regulation (biogenesis, processing, and dysregulation) of miRNAs and their role as modulators of the epigenetic machinery. We have also highlighted their potential clinical value, such as validated diagnostic and prognostic biomarkers, and their relevant role as chromatin modifiers in cancer therapy.
Highlights
Epigenetics refer to inheritable features that are related to alterations or changes outside the DNA nucleotide sequence, giving rise to changes in gene expression patterns
DNA methylation consists of the covalent addition of a methyl group in cytosine nucleotides (5-methylcytosine, 5-mC), usually within CpG dinucleotides that are concentrated in CpG islands
Lujambio et al demonstrated that hypermethylation of the miR-34b/c, miR-148a, and miR-9-3 CpG islands was significantly associated with the presence of lymph node metastasis in melanoma, lung, and breast cancer [133]
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. MicroRNAs (miRNAs) are 18–25-nucleotide-long, non-coding RNAs with critical roles in a variety of biological processes, such as proliferation, differentiation, or immune response They exert their function through the regulation of gene expression, mostly at the post-transcriptional level [1,2,3,4]. The pre-miRNA is processed in the cytoplasm by DICER, a RNAse III endonuclease, into an 18–25 nucleotide-long double-stranded RNA [16]. An example of the former is the so-called mirtron pathway, where an intronic sequence of a particular mRNA could function as pre-miRNA This intronic sequence is processed by the spliceosome, exported to the cytoplasm by XPO5 to continue with the canonical pathway via DICER to form a mature miRNA [24]. Another RNase III enzyme, Dicer, processes the pre-miRNA to generate a transient ~22-nucleotide miRNA: miRNA* duplex This duplex is loaded into the miRNAassociated multiprotein RNA-induced silencing complex (mi-RISC).
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