microRNAs Make the Call in Cancer Personalized Medicine

Abstract

Since their discovery and the advent of RNA interference, microRNAs have drawn enormous attention because of their ubiquitous involvement in cellular pathways from life to death, from metabolism to communication. It is also widely accepted that they possess an undeniable role in cancer both as tumor suppressors and tumor promoters modulating cell proliferation and migration, epithelial-mesenchymal transition and tumor cell invasion and metastasis. Moreover, microRNAs can even affect the tumor surrounding environment influencing angiogenesis and immune system activation and recruitment. The tight association of microRNAs with several cancer-related processes makes them undoubtedly connected to the effect of specific cancer drugs inducing either resistance or sensitization. In this context, personalized medicine through microRNAs arose recently with the discovery of single nucleotide polymorphisms in the target binding sites, in the sequence of the microRNA itself or in microRNA biogenesis related genes, increasing risk, susceptibility and progression of multiple types of cancer in different sets of the population. The depicted scenario implies that the overall variation displayed by these small non-coding RNAs have an impact on patient-specific pharmacokinetics and pharmacodynamics of cancer drugs, pushing on a rising need of personalized treatment. Indeed, microRNAs from either tissues or liquid biopsies are also extensively studied as valuable biomarkers for disease early recognition, progression and prognosis. Despite microRNAs being intensively studied in recent years, a comprehensive review describing these topics all in one is missing. Here we report an up-to-date and critical summary of microRNAs as tools for better understanding personalized cancer biogenesis, evolution, diagnosis and treatment.

Keywords: MiR-SNP; biomarker; cancer; microRNAs; personalized medicine.

Figure 1

Down- or up-regulation of microRNAs contribute to the cancer driving steps. Often one microRNA affects more than one hallmark, with one prevailing tissue-dependent mechanism.

Figure 2

miRSNP can affect microRNA biogenesis and activity. SNPs may be present on the microRNA decreasing (A) or increasing (B) its binding affinity for the target mRNA. SNPs may be present in the binding site of a target mRNA decreasing (C) or increasing (D) binding affinity (or creating new binding sites). In this last scenario are represented also SNPs in genes of the microRNA biogenesis machinery. These SNPs usually affect the regulation of the genes increasing or decreasing binding affinity of post-transcriptional regulators like microRNAs. SNPs may also affect the secondary structure of premature forms of the microRNAs decreasing (E) or increasing (F) their maturation.

Figure 3

Scheme of the multiple centrifugation steps performed in Duttagupta et al. (2011).