MicroRNAs: understanding their role in gene expression and cancer

Abstract

MicroRNAs are small RNA molecules that regulate gene expression in cells. These small molecules comprise 17 to 25 nucleotides and are able to recognize target messenger RNAs by sequence complementarity and regulate their protein translation. Different microRNAs are expressed in all human cells. There is over 2,500 microRNAs described in humans that are involved in virtually all biological processes. Given their role as gene expression regulators, these molecules have been widely investigated and are thought to be associated with some specific physiological and pathological conditions, being proposed as biomarkers. It has recently been reported that microRNAs are secreted outside cells and are involved in intercellular communication. MicroRNAs in biological fluids are named circulating and have been detected in all body fluids, although the expression profile is specific for each type. The major advantages of using circulating microRNAs as biological markers are the high stability of those molecules and the wide availability of samples. Also, given the individual nature of microRNA expression changes, these molecules have a high potential for use in personalized medicine. In fact, microRNA expression profile determination may support disease recognition and diagnosis, and can be used to monitor therapeutic responses and establish patient prognosis, assisting in choice of treatment. This review provides a general overview of microRNAs and discusses the importance of those molecules in cancer, for deeper understanding of their role in this disease.

Figure 1. Canonical microRNA biogenesis pathway. This pathway begins with nuclear transcription of microRNAs into molecules named pri-microRNAs. Pri-microRNAs are then processed by the nuclear enzyme Drosha to generate smaller molecules, the so-called pre-microRNAs. Pre-microRNAs are exported to the cytoplasm by exportin-5, then processed by the enzyme Dicer, giving rise to double-stranded microRNA molecules, which bind to RNA-induced silencing complex. The strands of bound microRNAs are then separated, originating to mature microRNAs, which are able to bind to messenger RNAs and inhibit their translation

Figura 1. Biogênese canônica de microRNAs. Os microRNAs são primeiramente traduzidos no núcleo em moléculas denominadas pri-microRNAs. A partir de sequências de DNA, os pri-microRNAs são processados pela enzima nuclear Drosha, dando origem a uma molécula menor, chamada pré-microRNA. O pré-microRNA é exportado ao citoplasma, com a ajuda da exportina-5, no qual será processado pela enzima Dicer, gerando uma molécula de microRNA de fita dupla, que se acoplará ao complexo proteico silenciador induzido por RNA. O microRNA associado ao complexo silenciador induzido por RNA terá suas fitas separadas, dando origem a microRNAs maduros e capazes de se ligar aos RNAs mensageiros, inibindo sua tradução