Role of microRNAs in translation regulation and cancer

Abstract

MicroRNAs (miRNAs) are pervasively expressed and regulate most biological functions. They function by modulating transcriptional and translational programs and therefore they orchestrate both physiological and pathological processes, such as development, cell differentiation, proliferation, apoptosis and tumor growth. miRNAs work as small guide molecules in RNA silencing, by negatively regulating the expression of several genes both at mRNA and protein level, by degrading their mRNA target and/or by silencing translation. One of the most recent advances in the field is the comprehension of their role in oncogenesis. The number of miRNA genes is increasing and an alteration in the level of miRNAs is involved in the initiation, progression and metastases formation of several tumors. Some tumor types show a distinct miRNA signature that distinguishes them from normal tissues and from other cancer types. Genetic and biochemical evidence supports the essential role of miRNAs in tumor development. Although the abnormal expression of miRNAs in cancer cells is a widely accepted phenomenon, the cause of this dysregulation is still unknown. Here, we discuss the biogenesis of miRNAs, focusing on the mechanisms by which they regulate protein synthesis. In addition we debate on their role in cancer, highlighting their potential to become therapeutic targets.

Keywords: MicroRNA, Translation, Cancer, OncomiR, Tumor suppressor

Core tip: MicroRNAs (miRNAs) are short non-coding RNAs (19-25 bp in length) which negatively regulate gene expression at the mRNA and protein level. By binding coding transcripts, miRNAs cause degradation or translation inhibition of their target genes and affect a multitude of biological processes, such as proliferation and tumor growth. In this review we critically analyze the mechanism of action of miRNAs and their potential role in cancer, opening a window on future perspectives for their use as novel therapeutic targets.