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, 34 (3), 363-70

Mechanisms and Role of microRNA Deregulation in Cancer Onset and Progression

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Mechanisms and Role of microRNA Deregulation in Cancer Onset and Progression

Edenir Inês Palmero et al. Genet Mol Biol.

Abstract

MicroRNAs are key regulators of various fundamental biological processes and, although representing only a small portion of the genome, they regulate a much larger population of target genes. Mature microRNAs (miRNAs) are single-stranded RNA molecules of 20-23 nucleotide (nt) length that control gene expression in many cellular processes. These molecules typically reduce the stability of mRNAs, including those of genes that mediate processes in tumorigenesis, such as inflammation, cell cycle regulation, stress response, differentiation, apoptosis and invasion. MicroRNA targeting is mostly achieved through specific base-pairing interactions between the 5' end ('seed' region) of the miRNA and sites within coding and untranslated regions (UTRs) of mRNAs; target sites in the 3' UTR diminish mRNA stability. Since miRNAs frequently target hundreds of mRNAs, miRNA regulatory pathways are complex. Calin and Croce were the first to demonstrate a connection between microRNAs and increased risk of developing cancer, and meanwhile the role of microRNAs in carcinogenesis has definitively been evidenced. It needs to be considered that the complex mechanism of gene regulation by microRNAs is profoundly influenced by variation in gene sequence (polymorphisms) of the target sites. Thus, individual variability could cause patients to present differential risks regarding several diseases. Aiming to provide a critical overview of miRNA dysregulation in cancer, this article reviews the growing number of studies that have shown the importance of these small molecules and how these microRNAs can affect or be affected by genetic and epigenetic mechanisms.

Keywords: cancer; epigenetic alteration; genetic alteration; microRNA; therapeutic application.

Figures

Figure 1
Figure 1
The biogenesis and function of miRNAs.
Figure 2
Figure 2
MicroRNAs (miRNAs) as tumour suppressors and oncogenes. Downregulation or loss of miRNAs with tumour suppressor function may increase translation of oncogenes and hence formation of excess oncogenic proteins, leading to tumour formation. In contrast, upregulation of oncogenic miRNAs may block tumour suppressor genes and also lead to tumour formation.
Figure 3
Figure 3
Possible mechanism for SNP within 3′UTR region of the messenger RNA (mRNA) target gene.
Figure 4
Figure 4
Crosstalk between genomic methylation, histone modifications and the effects of microRNAs in the gene expression profile.

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